Трансплантационные технологии и исследования

Many people make the generous decision to donate organs and tissue after death and, much more rarely, some make the heroic decision to donate an organ or tissue while alive. Others suffer major organ failure and make a decision to receive an organ or tissue. Some choose to be involved in medical practice or medical research involving the use of donated organs and tissues. The issues involved in transplantation have become increasingly complex including the development of the ability to culture tissues, the development of bio banks, xenotransplantation and human-animal transgenesis and the effects of trade in human tissue products

With the introduction of the MELD score for the allocation of orthotopic liver transplant (OLT) in February 2002, a striking 278% increase in the number of simultaneous liver-kidney transplants (SLKT) was observed during the 9-year period post-MELD when compared with the preceeding 9-year in the pre-MELD era (pre- vs.post-MELD era, n= 1049 vs. 2914, respectively) [1]. For OLT candidates with simultaneous end-stage kidney failure, SLKT is a well-established effective therapeutic option for virtually all suitable candidates.However, there have been no well-defined guidelines to determine whether a kidney transplant should be offered to OLT candidates who have chronic kidney disease (CKD) or prolonged acute kidney injury (AKI) secondary to hepatorenal syndrome (HRS) or acute tubular necrosis (ATN) while awaiting a liver transplant. Specific challenges in the decision making process include the accurate assessment of the degree of existing renal dysfunction in those with CKD and the prediction of the extent of renal function recovery in those with AKI with or without underlying CKD.

The polyomavirus JC virus (JCV) is a small nonenveloped DNA virus that asymptomatically infects about 80% of healthy adults and establishes latency in the kidney tissue. In case of immunodeficient hosts, JCV can lytically infect the oligodendrocytes, causing a fatal demyelinating disease, known as Progressive Multifocal Leukoencephalopathy (PML). Although the reactivation of another human polyomavirus, BK Virus (BKV), is relatively common and its association with the Polyomavirus Associated Nephropathy (PVAN) following renal transplantation is assessed, JCV replication and its impact on graft function and survival is less well studied. In addition, none of the performed studies
ruled out the hypothesis that JCV could be associated with certain post-transplantation clinical syndromes. Thus, monitoring of Polyomaviruses infection, especially during the first 24 months post-transplantation, is recommended.

Human multipotent mesenchymal stromal cells (hMSCs) represent stem cells for non-hematopoietic tissues. The main interest in hMSCs is correlated with their ability to suppress the proliferation of CD8+ T lymphocytes regulating the transplantation rejection. Moreover, hMSCs are able to inhibit the differentiation of dendritic cells, the proliferation and antibody production of B lymphocytes and they stimulate the formation of regulatory T cells. The mechanisms at the basis of MSCs activity need cell-cell interaction and the secretion of soluble molecules into the microenvironment as hepatocyte growth factor, transforming growth factor-beta (TGF-beta), interleukin-10 and -2 (IL-10, IL-2), tumour necrosis factor-alpha (TNF-alpha), prostaglandin E2 (PGE2), indoleamine 2,3-dioxygenase (IDO) and Human Leukocyte Antigen (HLA)-G

The currently used immunosuppressive drugs have a narrow therapeutic index which required to individualize the dose regimen for different recipients. Pharmacogenetic is the use of genetic screening to prevent metabolic responses to different immunosuppressive drugs. Since the oxidative enzymes cytochrome P450 CYP3A and the drug efflux pump P-glycoprotein (P-gp) play a pivotal role in immunosuppressive drugs metabolism, pharmacogenetic studies have been mainly focused on these two enzymes. This would provide an important aid toward drug regimen individualization during the post-transplant therapy and has potential to improve graft outcom