1, 2, 3 Cell-based therapy, especially stem cells, provides new hope for patients suffering from incurable diseases where treatment approaches focus on management of the disease not treat it. The successful approval of cancer immunotherapies in the US and mesenchymal stem cell (MSC)-based therapies in Europe have turned the wheel of regenerative medicine to become prominent treatment modalities. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. Penning of the faculty of Veterinary Sciences.Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. The dog liver stem cell transplantation project was co-financed by ZonMW ( 116004121), under responsibility of Dr Louis C. I hope that we can treat the first patient with a liver stem cell transplantation in five years from now.’ The collaboration in regenerative medicine between researchers in the fields of human and veterinary medicine enables fantastic cross-fertilisation. ‘I really believe that it should be possible. Dogs resemble children in terms of body weight and liver function.’ Fuchs feels confident about the method. ‘If we can manage to increase the efficiency in the future, then we could also translate this technique into human medicine. When we had around a billion healthy cells, we put the cells back in the liver of the same dog.’ The transplantation succeeded and proved to be healthy: no complications occurred. In the lab we selected the stem cells, corrected the genetic defect in these and stimulated them to multiply very often. Kruitwagen explains: ‘We took a small biopsy from the dogs’ livers. Nonetheless, the fact that the transplantation of the stem cells succeeded in the six dogs is a good step forward in itself. ‘When it comes to metabolic diseases, such as the illness affecting these six dogs, you often need just five to ten percent of liver function in order to treat the patients’ symptoms, so we could treat the disease by just replacing a small part of the liver cells.’ That’s our biggest goal.’ However, she does stress that it’s not necessary to achieve a 100 percent recovery of the liver. ‘The transplantation efficiency still needs to be dramatically improved. After two years, they found only a small proportion of the transplanted cells still surviving in the liver. We hoped that the healthy stem cells would divide, and that they would outgrow the diseased cells.’ Unfortunately for the researchers, that didn’t happen. That’s one percent of the total number of cells in a dog liver. Kruitwagen continues: ‘Together with a colleague at the Faculty of Veterinary Medicine, molecular biologist Bart Spee, we transplanted around a billion healthy stem cells into the livers of six dogs. However, the transplantation of stem cells is currently not efficient enough to allow treatment, as shown by Fuchs’ and Kruitwagen’s work. Veterinarian and scientist Hedwig Kruitwagen Improving transplantation efficiency
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