Abstract
The successful transplantation of human materials such as organs, tissues and cells into patients does not only depend on the benefits, but also on the mitigation of risks. To gain insight into recent publications on risks associated with the process of transferring human materials from donor to recipient we performed a horizon scan by reviewing scientific literature and news websites of 2011 on this subject. We found there is ample information on how extended donor criteria, such as donor age, affect the survival rates of organs or patients. Interestingly, gender mismatch does not appear to be a major risk factor in organ rejection. Data on risks of donor tumor transmission was very scarce; however, risk categories for various tumor types have been suggested. In order to avoid rejection, a lot of research is directed towards engineering tissues from a patient’s own tissues and cells. Some but not all of these developments have reached the clinic. Developments in the field of stem cell therapy are rapid. However, many hurdles are yet to be overcome before these cells can be applied on a large scale in the clinic. The processes leading to genetic abnormalities in cells differentiated from stem cells need to be identified in order to avoid transplantation of aberrant cells. New insights have been obtained on storage and preservation of human materials, a critical step for success of their clinical use. Likewise, quality management systems have been shown to improve the quality and safety of human materials used for transplantation.
Similar content being viewed by others
Notes
The EU Directives 2004/23/EC, 2006/17/EC, 2006/86/EC.
The EU Directives 2004/23/EC, 2006/17/EC, 2006/86/EC).
National Health Service Blood and Transplant.
References
Akkina SK, Asrani SK et al (2012) Development of organ-specific donor risk indices. Liver Transpl 18(4):395–404
Alencar S, Garnica M et al (2010) Cryopreservation of peripheral blood stem cell: the influence of cell concentration on cellular and hematopoietic recovery. Transfusion 50(11):2402–2412
Ambasudhan R, Talantova M et al (2011) Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell 9(2):113–118
Amps K, Andrews PW, et al (2011) Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage. Nat Biotechnol 29(12):1132–1144
Anguita-Compagnon AT, Dibarrart MT, et al (2010) Mobilization and collection of peripheral blood stem cells: guidelines for blood volume to process, based on CD34-positive blood cell count in adults and children. Transplant Proc 42(1):339–344
Anokye-Danso F, Trivedi CM et al (2011) Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 8(4):376–388
Antonenas V, Garvin F et al (2006) Fresh PBSC harvests, but not BM, show temperature-related loss of CD34 viability during storage and transport. Cytotherapy 8(2):158–165
Avolio AW, Cillo U et al (2011) Balancing donor and recipient risk factors in liver transplantation: the value of D-MELD with particular reference to HCV recipients. Am J Transplant 11(12):2724–2736
Bacchella T, Galvão FH et al (2008) Marginal grafts increase early mortality in liver transplantation. Sao Paulo Med J 126(3):161–165
Blumberg EA (2011) Creating a safer donor: a quarter century of progress? Am J Transplant 11(6):1117–1118
Bronzatto EJM, da Silva Quadros KR, et al (2009) Delayed graft function in renal transplant recipients: risk factors and impact on 1-year graft function: a single center analysis. Transplant Proc 41(3):849–851
Brubaker SA, Wilson D (2010) Coding and traceability: cells and tissues in North America. Cell Tissue Bank 11(4):379–389
Bruzzone P, Giannarelli D et al (2011) Extended criteria liver donation and transplant recipient consent: the European experience. Transplant Proc 43(4):971–973
Busche MN, Knobloch K et al (2011) Solid organ procurement from donors with carbon monoxide poisoning and/or burn—a systematic review. Burns 37(5):814–822
Cassini MF, Cologna AJ, et al (2010) Why not to use kidney grafts from elderly donors.Transplant Proc 42(2):417–420
Chandrasekar A, Warwick RM et al (2011) Exclusion of deceased donors post-procurement of tissues. Cell Tissue Bank 12(3):191–198
Cheah PL, Ong CW et al (2011) Microbial contamination of autologous peripheral blood stem cell products: incidence, clinical outcome, quality control and management strategies. Pathology 43(4):340–345
Christodoulou C, Longmire TA et al (2011) Mouse ES and iPS cells can form similar definitive endoderm despite differences in imprinted genes. J Clin Invest 121(6):2313–2325
ClinicalTrials gov identifier: NCT01305863 (2011) Feasibility study of the TGI adipose-derived stromal cell (ASC)-coated ePTFE vascular graft (TGI-PVG-IDE). http://clinicaltrials.gov/ct2/show/NCT01305863. Accessed 17 June 2013
Cockbain AJ, Jacob M, et al (2011) Transplantation of solid organs procured from influenza A H1N1 infected donors. Transpl Int 24(12):107–110
Collins MG, Chang SH et al (2009) Outcomes of transplantation using kidneys from donors meeting expanded criteria in Australia and New Zealand, 1991 to 2005. Transplantation 87(8):1201–1209
Council Directive (EC) 2004/23/EC of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells
Council Directive (EC) 2010/45/EC of 7 July 2010 on standards of quality and safety of human organs intended for transplantation
Cravedi P, Ruggenenti P et al (2011) Old donors for kidney transplantation: how old? Gerontology 57(6):513–520
de Lau W, Barker N et al (2011) Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476(7360):293–297
Delmonico FL (2011) Transplantation: can kidneys donated after cardiac death save lives? Nat Rev Nephrol 7(1):5–6
Di Cocco P, Orlando G et al (2011) Kidney transplantation from older donors. Transplant Proc 43(4):1033–1035
Dickinson AM, Charron D (2005) Non-HLA immunogenetics in hematopoietic stem cell transplantation. Curr Opin Immunol 17(5):517–525
Dickinson AM, Pearce KF et al (2010) Impact of genomic risk factors on outcome after hematopoietic stem cell transplantation for patients with chronic myeloid leukemia. Haematologica 95(6):922–927
Domagala P, Kwiatkowski A et al (2009) Assessment of kidneys procured from expanded criteria donors before transplantation. Transplant Proc 41(8):2966–2969
Dominguez-Gil B, Haase-Kromwijk B, et al (2011) Current situation of donation after circulatory death in European countries. Transpl Int 24(7):676–686
Donmez A, Kabaroglu C et al (2012) The difference in lactate dehydrogenase activity between pre-and post-mobilization periods is a good indicator of successful stem cell mobilization. Transfus Apheres Sci 48(1):83–86
Dzamukova MR, Zamaleeva AI et al (2011) A direct technique for magnetic functionalization of living human cells. Langmuir 27(23):14386–14393
Eastlund T (2006) Bacterial infection transmitted by human tissue allograft transplantation. Cell Tissue Bank 7(3):147–166
Ellingson K, Seem D et al (2011) Estimated risk of human immunodeficiency virus and hepatitis C virus infection among potential organ donors from 17 organ procurement organizations in the United States. Am J Transplant 11(6):1201–1208
Evenson AR (2011) Utilization of kidneys from donation after circulatory determination of death. Curr Opin Organ Transpl 16(4):385
Feng S, Goodrich NP et al (2006) Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant 6(4):783–790
Foley DP, Fernandez LA et al (2011) Biliary complications after liver transplantation from donation after cardiac death donors: an analysis of risk factors and long-term outcomes from a single center. Ann Surg 253(4):817–825
Folgiero V, Migliano E et al (2010) Purification and characterization of adipose-derived stem cells from patients with lipoaspirate transplant. Cell Transplant 19(10):1225–1235
Forni A, Luciani GB et al (2010) Impact of donor quality on outcome of heart transplantation. Eur J Cardiothorac Surg 38(6):788–794
Forni A, Luciani GB et al (2011) Results with expanded donor acceptance criteria in heart transplantation. Transplant Proc 43(4):953–959
Gahrton G (2007) Risk assessment in haematopoietic stem cell transplantation: impact of donor-recipient sex combination in allogeneic transplantation. Best Pract Res Clin Haematologica 20:219
Gratwohl A, Brand R et al (2011) Introduction of a quality management system and outcome after hematopoietic stem-cell transplantation. J Clin Oncol 29(15):1980–1986
Gude E, Andreassen AK et al (2010) Acute renal failure early after heart transplantation: risk factors and clinical consequences. Clin Transplant 24(6):E207–E213
Gurbanov E, Meng X et al (2011) Evaluation ECMO in adult cardiac transplantation: can outcomes of marginal donor hearts be improved? J Cardiovasc Surg 52(3):419–427
Hirai H, Tani T et al (2011) Radical acceleration of nuclear reprogramming by chromatin remodeling with the transactivation domain of MyoD. Stem Cells 29(9):1349–1361
Ho STB, Tanavde VM et al (2011) Upregulation of adipogenesis and chondrogenesis in MSC serum-free culture. Cell Med Part B Cell Transpl 2(1):27–41
Hong JC, Yersiz H et al (2011) Liver transplantation using organ donation after cardiac death: a clinical predictive index for graft failure-free survival. Arch Surg 146(9):1017–1023
Hoogland ER, Snoeijs MGJ et al (2010) DCD kidney transplantation: results and measures to improve outcome. Curr Opin Organ Transpl 15(2):177
Hovatta O (2011) Infectious problems associated with transplantation of cells differentiated from pluripotent stem cells. Semin Immunopathol 33(6):627–630
Hubel A, Carlquist D et al (2004) Liquid storage, shipment, and cryopreservation of cord blood. Transfusion 44(4):518–525
Humar A, Lebranchu Y et al (2010) The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Am J Transplant 10(5):1228–1237
Ilic D, Stephenson E et al (2012) Derivation and feeder-free propagation of human embryonic stem cells under xeno-free conditions. Cytotherapy 14(1):122–128
Ison MG, Hager J et al (2009) Donor-derived disease transmission events in the United States: data reviewed by the OPTN/UNOS disease transmission advisory committee. Am J Transplant 9(8):1929–1935
Ison MG, Llata E et al (2011) Transmission of human immunodeficiency virus and hepatitis C virus from an organ donor to four transplant recipients. Am J Transplant 11(6):1218–1225
Jochmans I, Pirenne J (2011) Graft quality assessment in kidney transplantation: not an exact science yet! Curr Opin Organ Transpl 16(2):174–179
Karatzas T, Bokos J, et al (2011) Advanced donor age alone is not a risk factor for graft survival in kidney transplantation.Transplant Proc 43(5):1537–1543
Karp SJ, Johnson S et al (2011) Minimising cold ischaemic time is essential in cardiac death donor-associated liver transplantation. HPB 13(6):411–416
Kim J, Efe JA et al (2011a) Direct reprogramming of mouse fibroblasts to neural progenitors. Proc Natl Acad Sci USA 108(19):7838–7843
Kim TK, Sul JY et al (2011b) Transcriptome transfer provides a model for understanding the phenotype of cardiomyocytes. Proc Natl Acad Sci USA 108(29):11918–11923
Klein MA, Kadidlo D et al (2006) Microbial contamination of hematopoietic stem cell products: incidence and clinical sequelae. Biol Blood Marrow Transpl 12(11):1142–1149
Kucirka LM, Sarathy H et al (2011) Risk of window period HIV infection in high infectious risk donors: systematic review and meta-analysis. Am J Transplant 11(6):1176–1187
Kudo Y, Minegishi M et al (2011) Quality assessment of umbilical cord blood units at the time of transplantation. Int J Hematol 93(5):645–651
Kullberg-Lindh C, Mellgren K et al (2011) Opportunistic virus DNA levels after pediatric stem cell transplantation: serostatus matching, anti-thymocyte globulin, and total body irradiation are additive risk factors. Transpl Infect Dis 13(2):122–130
Lai JC, Feng S et al (2011) Gender differences in liver donor quality are predictive of graft loss. Am J Transplant 11(2):296–302
Lapasset L, Milhavet O et al (2011) Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes Dev 25(21):2248–2253
Laurent LC, Ulitsky I et al (2011) Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell 8(1):106–118
Leithead JA, Tariciotti L, et al (2012) Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury. Am J Transplant 12(4):965–975
Li W, Sun W et al (2011a) Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors. Proc Natl Acad Sci USA 108(20):8299–8304
Li Z, Yang C-S et al (2011b) Small RNA-mediated regulation of iPS cell generation. EMBO J 30(5):823–834
Lister R, Pelizzola M, et al (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells (1476–4687 (Electronic))
Lonze BE, Dagher NN et al (2011) Outcomes of renal transplants from centers for disease control and prevention high-risk donors with prospective recipient viral testing: a single-center experience. Arch Surg 146(11):1261
Lootens N, De Smet S et al (2004) Viable CD34 + stem cell content of a cord blood graft: which measurement performed before transplantation is most representative? Transfusion 44(4):547–554
Lowder JN, Whelton P (2003) Microbial contamination of cellular products for hematolymphoid transplantation therapy: assessment of the problem and strategies to minimize the clinical impact. Cytotherapy 5(5):377–390
Lyn TE (2011) Stem cell team aims for spare heart parts in five years. Reuters online, 18 Aug 2011
Lysak D, Koristek Z et al (2011) Efficacy and safety of peripheral blood stem cell collection in elderly donors; does age interfere? J Clin Apheresis 26(1):9–16
Malinoski DJ, Daly MC, et al (2011) Achieving donor management goals before deceased donor procurement is associated with more organs transplanted per donor. J Trauma 71(4):990–995; discussion 996
Maluf DG, Edwards EB et al (2009) Impact of the donor risk index on the outcome of hepatitis C virus–positive liver transplant recipients. Liver Transpl 15(6):592–599
Minegishi M, Itoh T et al (2007) Quality of umbilical cord blood CD34+ cells in a double-compartment freezing bag cryopreserved without a rate-controlled programmed freezer. Int J Hematol 85(1):78–84
Miura J, Minegishi M et al (2008) Quality evaluation of umbilical cord blood progenitor cells cryopreserved with a small-scale automated liquid nitrogen system. Cryobiology 57(2):178–181
Moog R (2010) Peripheral blood stem cell collection in children: management, techniques and safety. Transfus Apheresis Sci 43(2):203–205
Moreira P, Sa H et al (2011) Delayed renal graft function: risk factors and impact on the outcome of transplantation. Transplant Proc 43(1):100–105
Nalesnik MA, Woodle ES et al (2011) Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. Am J Transplant 11(6):1140–1147
Nannya Y, Kataoka K et al (2011) The negative impact of female donor/male recipient combination in allogeneic hematopoietic stem cell transplantation depends on disease risk. Transpl Int 24(5):469–476
Ozhathil DK, Li YF et al (2011) Impact of center volume on outcomes of increased-risk liver transplants. Liver Transpl 17(10):1191–1199
Paliwal P, Conboy IM (2011) Inhibitors of tyrosine phosphatases and apoptosis reprogram lineage-marked differentiated muscle to myogenic progenitor cells. Chem Biol 18(9):1153–1166
Pang ZP, Yang N et al (2011) Induction of human neuronal cells by defined transcription factors. Nature 476(7359):220–223
Pasi CE, Dereli-Oz A et al (2011) Genomic instability in induced stem cells. Cell Death Differ 18(5):745–753
Phanstiel DH, Brumbaugh J et al (2011) Proteomic and phosphoproteomic comparison of human ES and iPS cells. Nat Meth 8(10):821–827
Pine JK, Aldouri A et al (2009) Liver transplantation following donation after cardiac death: an analysis using matched pairs. Liver Transpl 15(9):1072–1082
Pizanis N, Heckmann J et al (2010) Lung transplantation using donors 55 years and older: is it safe or just a way out of organ shortage? Eur J Cardiothorac Surg 38(2):192–197
Pizanis N, Petrov A et al (2012) A new preservation solution for lung transplantation: evaluation in a porcine transplantation model. J Heart Lung Transplant 31(3):310–317
Premasathian N, Avihingsanon Y et al (2010) Risk factors and outcome of delayed graft function after cadaveric kidney transplantation: a report from the Thai Transplant Registry. Transplant Proc 42(10):4017–4020
Qiang L, Fujita R et al (2011) Directed conversion of Alzheimer’s disease patient skin fibroblasts into functional neurons. Cell 146(3):359–371
Queen’s University (2011) Extracting stem cells from fat for tissue regeneration. http://www.queensu.ca/news/articles/extracting-stem-cells-fat-tissue-regeneration. Accessed 17 June 2013
Quinlan AR, Boland MJ et al (2011) Genome sequencing of mouse induced pluripotent stem cells reveals retroelement stability and infrequent DNA rearrangement during reprogramming. Cell Stem Cell 9(4):366–373
Reinhardt J, Stuhler A et al (2011) Safety of bovine sera for production of mesenchymal stem cells for therapeutic use. Hum Gene Ther 22(6):775
Richa E (2011) The correlation between the granulocyte content in infused stem cells and side effects of the infusion. Blood Transfus 9(3):346
Rodríguez-Arias D, Wright L et al (2010) Success factors and ethical challenges of the Spanish Model of organ donation. The Lancet 376(9746):1109–1112
Saha K, Mei Y et al (2011) Surface-engineered substrates for improved human pluripotent stem cell culture under fully defined conditions. Proc Natl Acad Sci USA 108(46):18714–18719
Saik JE, Gould DJ et al (2011) Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly(ethylene glycol) hydrogels. Acta Biomater 7(1):133–143
Salvalaggio PR, Dzebisashvili N et al (2011) The interaction among donor characteristics, severity of liver disease, and the cost of liver transplantation. Liver Transpl 17(3):233–242
Santamaria X, Massasa EE et al (2011) Derivation of insulin producing cells from human endometrial stromal stem cells and use in the treatment of murine diabetes. Mol Ther 19(11):2065–2071
Saraswathula A, Chen S, et al (2010) Functional, insulin-secreting pancreatic endoderm derived from human spermatogenial stem cells. American Society for cell biology’s 50th annual meeting, December 12, 2010
Sarig R, Rotter V (2011) Can an iPS cell secure its genomic fidelity? Cell Death Differ 18(5):743–744
Sarkar D, Ankrum JA et al (2011a) Cellular and extracellular programming of cell fate through engineered intracrine-, paracrine-, and endocrine-like mechanisms. Biomaterials 32(11):3053–3061
Sarkar D, Spencer JA et al (2011b) Engineered cell homing. Blood 118(25):e184–e191
Schönberger S, Meisel R et al (2010) Prospective, comprehensive, and effective viral monitoring in children undergoing allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 16(10):1428–1435
Sen GL (2011) Remembering one’s identity: the epigenetic basis of stem cell fate decisions. FASEB J 25(7):2123–2128
Sensebé L, Bourin P et al (2010) Good manufacturing practices production of mesenchymal stem/stromal cells. Hum Gene Ther 22(1):19–26
Shu Z, Kang X et al (2010) Development of a reliable low-cost controlled cooling rate instrument for the cryopreservation of hematopoietic stem cells. Cytotherapy 12(2):161–169
Song B, Niclis JC et al (2011) Generation of induced pluripotent stem cells from human kidney mesangial cells. J Am Soc Nephrol 22(7):1213–1220
Soo A, Healy DG et al (2011) Quality control in homograft valve processing: when to screen for microbiological contamination? Cell Tissue Bank 12(3):185–190
Stephenson E, Ogilvie CM et al (2010) Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells. J R Soc Interface 7(Suppl 6):S677–S688
Strong DM, Seem D et al (2010) Development of a transplantation transmission sentinel network to improve safety and traceability of organ and tissues. Cell Tissue Bank 11(4):335–343
Thesleff T, Lehtimaki K et al (2011) Cranioplasty with adipose-derived stem cells and biomaterial: a novel method for cranial reconstruction. Neurosurgery 68(6):1535–1540
T’Joen V, De Grande L et al (2011) An efficient, economical slow-freezing method for large-scale human embryonic stem cell banking. Stem Cells Dev 21(5):721–728
Tremolada C, Palmieri G et al (2010) Adipocyte transplantation and stem cells: plastic surgery meets regenerative medicine. Cell Transplant 19(10):1217–1223
Tsutsui H, Valamehr B et al (2011) An optimized small molecule inhibitor cocktail supports long-term maintenance of human embryonic stem cells. Nat Commun 2:167
Turovets N, Fair J et al (2012) Derivation of high-purity definitive endoderm from human parthenogenetic stem cells using an in vitro analog of the primitive streak. Cell Transplant 21(1):217–234
University Of Gothenburg (2011) Stem cell technology used in unique surgery. http://www.sahlgrenska.gu.se/english/news_and_events/news/News_Detail/stem-cell-technology-used-in-unique-surgery.cid991966. Accessed 17 June 2013
UMC St Radboud (2011) Weefseltechnologie voor urologische problemen. Retrieved 21 January, 2011
van Wijk MJ, Poniatowski S, et al (2011a) Results of the clinical donor case and quality system case workshops of the European Association of Tissue Banks annual meeting 2009. Cell Tissue Bank 13(1):191–202
van Wijk MJ, van Geyt C, et al (2011) Physical examination of potential tissue donors: results of a risk management procedure to identify the critical elements of the physical examination. Cell Tissue Bank 13:547–563
Vitale A, Ramirez Morales R et al (2011) Donor-model for end-stage liver disease and donor-recipient matching in liver transplantation. Transplant Proc 43(4):974–976
Wang JMG, Montgomery RA et al (2011a) Incompatible live-donor kidney transplantation in the United States: results of a national survey. Clin J Am Soc Nephrol 6(8):2041–2046
Wang YC, Nakagawa M et al (2011b) Specific lectin biomarkers for isolation of human pluripotent stem cells identified through array-based glycomic analysis. Cell Res 21(11):1551–1563
Watson CJ, Bradley JA (2011) Evaluating the risk of cancer transmission to optimize organ usage. Am J Transplant 11(6):1113–1114
Weber K, Thomaschewski M et al (2011) RGB marking facilitates multicolor clonal cell tracking. Nat Med 17(4):504–509
Yamamoto S, Ikeda H et al (2011) Quality of long-term cryopreserved umbilical cord blood units for hematopoietic cell transplantation. Int J Hematol 93(1):99–105
Zhou T, Benda C et al (2011) Generation of induced pluripotent stem cells from urine. J Am Soc Nephrol 22(7):1221–1228
Zou S (2004) Probability of viremia with HBV, HCV, HIV and HTLV among tissue donors in the United States. New Eng J Med 351(8):751–759
Acknowledgments
This investigation has been performed by order and for the account of the Health Care Inspectorate of the Netherlands, and is part of an ongoing horizon scanning system for new and emerging medical products.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Herberts, C.A., Park, M.V.D.Z., Pot, J.W.G.A. et al. Results from a horizon scan on risks associated with transplantation of human organs, tissues and cells: from donor to patient. Cell Tissue Bank 16, 1–17 (2015). https://doi.org/10.1007/s10561-014-9450-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10561-014-9450-0