Concern over kidney disease has increased dramatically in recent years within the medical community. It is estimated that approximately one in fifteen Americans, nearly 20 million people, experience chronic kidney disease with most of those diagnosed progressing to kidney failure. The ultimate treatment available for end stage renal failure is whole kidney transplantation. However, there are very few kidneys available for patients to receive and those patients who are fortunate enough to receive an organ must remain on immunosuppressive medication for the remainder of their lives. The United States Department of Health & Human Services have reported that 18 people die every day while on the waiting list for organ donations. The treatment is fairly successful as 69% of patients who receive a kidney transplant are still alive 5 years after the transplant. Tissue engineered organs could be a promising alternative for whole organ transplantation. The overall objective is to repopulate appropriate decellularized scaffolds from pigs, which are not immunogenic, with a patient's own cells to achieve a functional organ. Therefore, there would be an inexhaustible source of organs ready for transplantation without the risk of immune rejection. The naturally obtained scaffolds devoid of immunogens are a potential matrix to create artificial kidneys. Repopulation of decellularized rat kidneys with renal progenitor cells has been reported in previous studies. This dissertation reports the scale-up of the previous technology and building of partially functional human-sized kidneys. In the first step, we investigated various cell lysing agents and developed an automated decellularization procedure for whole porcine kidney decellularization. We also developed a preservation method for native and decellularized kidneys to avoid spoilage before and after decellularization. We also developed a decontamination procedure for whole porcine kidneys. Finally, we recellularized whole porcine kidney scaffolds with renal epithelial cells and achieved partial repopulation of the renal structure.

The causative role of the huntingtin (HTT) gene in Huntington's disease (HD) has been identified more than 25 years ago. The extension of CAG repeat stretch over 39 repeats in exon 1 of one HTT allele results in full penetrance of this neurodegenerative disorder. While the identification of the causative mutation raised hopes that development of the therapeutic compound will be easily achievable, the patients and their families are still waiting for treatment until now. The main reason for that might be the complex cellular function HTT that makes the determination of the pathologic mechanism difficult and the development of treatments even more challenging. Although a lot of different animal models have been generated until now, establishing a suitable model has still not been achieved yet. Due to its anatomy, physiology, and genetics, the minipig seems to be a suitable candidate for neurodegenerative disease models. Indeed, the existing Transgenic (Tg) Libechov minipig model manifests signs typical for HD in patients, but on the other hand significant inconsistencies have also been observed. The finding of malformation that partially shows the situation in human patients is true for both, the male reproductive tract as well as for the brain. The reason for this might be the fact the genetic...

The causative role of the huntingtin (HTT) gene in Huntington's disease (HD) has been identified more than 25 years ago. The extension of CAG repeat stretch over 39 repeats in exon 1 of one HTT allele results in full penetrance of this neurodegenerative disorder. While the identification of the causative mutation raised hopes that development of the therapeutic compound will be easily achievable, the patients and their families are still waiting for treatment until now. The main reason for that might be the complex cellular function HTT that makes the determination of the pathologic mechanism difficult and the development of treatments even more challenging. Although a lot of different animal models have been generated until now, establishing a suitable model has still not been achieved yet. Due to its anatomy, physiology, and genetics, the minipig seems to be a suitable candidate for neurodegenerative disease models. Indeed, the existing Transgenic (Tg) Libechov minipig model manifests signs typical for HD in patients, but on the other hand significant inconsistencies have also been observed. The finding of malformation that partially shows the situation in human patients is true for both, the male reproductive tract as well as for the brain. The reason for this might be the fact the genetic...