ABSTRACT
In cases of chronic renal insufficiency, successful kidney transplantation is the method of choice to restore patients' health, well-being and physical fitness. The interdisciplinary collaboration of nephrologists and transplant surgeons has always been a prerequisite for the successful pre-, peri- and post-transplant care of renal transplant patients. The same holds true for liver transplant patients. Here the nephrologist is often involved in cases requiring pre- or post-transplant dialysis as well as in decision making for combined liver-kidney transplantation. This review focuses on nephrological aspects in patient care before and after kidney and liver transplantation.
Subject(s)
Interdisciplinary Communication , Intersectoral Collaboration , Kidney Transplantation , Liver Transplantation , Patient Care Team , Graft Rejection/diagnosis , Graft Rejection/therapy , Humans , Postoperative Complications/diagnosis , Postoperative Complications/therapy , Primary Graft Dysfunction/diagnosis , Primary Graft Dysfunction/therapyABSTRACT
Essentials Platelet phenotypes can be modified by lentiviral transduction of hematopoietic stem cells. Megakaryocyte-specific lentiviral vectors were tested in vitro and in vivo for restricted expression. The glycoprotein 6 vector expressed almost exclusively in megakaryocytes. The platelet factor 4 vector was the strongest but with activity in hematopoietic stem cells. SUMMARY: Background Lentiviral transduction and transplantation of hematopoietic stem cells (HSCs) can be utilized to modify the phenotype of megakaryocytes and platelets. As the genetic modification in HSCs is transmitted onto all hematopoietic progenies, transgene expression from the vector should be restricted to megakaryocytes to avoid un-physiologic effects by ectopic transgene expression. This can be achieved by lentiviral vectors that control expression by lineage-specific promoters. Methods In this study, we introduced promoters of megakaryocyte/platelet-specific genes, namely human glycoprotein 6 (hGP6) and hGP9, into third generation lentiviral vectors and analyzed their functionality in vitro and in vivo in bone marrow transplantation assays. Their specificity and efficiency of expression was compared with lentiviral vectors utilizing the promoters of murine platelet factor 4 (mPf4) and hGP1BA, both with strong activity in megakaryocytes (MKs) used in earlier studies, and the ubiquitously expressing phosphoglycerate kinase (hPGK) and spleen focus forming virus (SFFV) enhancer/promoters. Results Expression from the mPf4 vector in MKs and platelets was the strongest similar to expression from the viral SFFV promoter, however, the mPf4 vector, also exhibited considerable off-target expression in hematopoietic stem and progenitor cells. In contrast, the newly generated hGP6 vector was highly specific to megakaryocytes and platelets. The specificity was also retained when reducing the promoter size to 350 bp, making it a valuable new tool for lentiviral expression in MKs/platelets. Conclusion MK-specific vectors express preferentially in the megakaryocyte lineage. These vectors can be applied to develop murine models to study megakaryocyte and platelet function, or for gene therapy targeting proteins to platelets.