Foetal Organ Implantation into Adult Animals: A Model for In Vivo Culture of stem cells?

Abstract

Background: Presently stem cell implantations are more and more developed and applied in clinics as alternative and complementary solutions to adult organ transplantation because of the growing demand and capacities to provide these interventions, while lack of donors is patent. But some limitations of stem cell use remain (for instance integration within the recipient organism of engineered tissues and organoids obtained in vitro from stem cells). The use of foetal organ implantation into adult animals may be an alternative for in vivo study of stem cell development and evaluation of the host participation to this process. The objectives of this work were to try different foetal organ implantations into adult animals (part I) and to evaluate their use for repairing experimental lesions of some adult organs (part II). Material and Methods: Part I: In > 650 experiments on rats and mice, different sites of foetal organ syngeneic implantation were proposed. Physiological (electric activity, motor and secretion activity) and morphological (per illumination, ultra sound and magnetic imaging, optic and electron microscopy) methods were used for implant development evaluation during up to 12 months. Part II: Foetal heart and foetal digestive organs were tested for both oesophagus circular defect and heart thermic lesion repair (38 and 29 rats).Trials with foetal pancreas implantation were provided in rats with diabetes induced by Streptozotocin and/or protein deficit and in a small pilot group of diabetic patients. Result: Part I: After a “dedifferentiation” phase, foetal organ implants could grow following ontogenetic pattern but – at least in our experimental conditions - some of them were not able to re-organize as a whole functional adult organ. The factors enhancing or limiting the organoid formation are considered. Part II: Foetal heart implants were proved to enhance heart lesion morphological and functional repair. Foetal oesophagus, stomach or intestine fragments combined with chitosan flaps ensured a complete restoration of the oesophagus wall after oval or segmental resection. Implantation of foetal pancreas was able to reverse Streptozotocin induced diabetes and to prevent chronic glucose disorders following protein deprivation in rats. In patients temporary positive influence was noted. Conclusion: Implantation of different foetal organs into syngeneic adults may constitute a valuable model for theoretical studies of in vivo stem cell differentiation and organoid growth. The ear implantation site deserves special attention. Some interesting applications are possible and worthwhile to be discussed and developed.