The use of autologous (or syngeneic) cells derived from induced pluripotent stem cells (iPSCs) holds great promise for future clinical use in a wide range of diseases and injuries. It is expected that cell replacement therapies using autologous cells would forego the need for immunosuppression, otherwise required in allogeneic transplantations. However, recent studies have shown the unexpected immune rejection of undifferentiated autologous mouse iPSCs after transplantation. Whether similar immunogenic properties are maintained in iPSC-derived lineage-committed cells (such as neural precursors) is relatively unknown. We demonstrate that syngeneic porcine iPSC-derived neural precursor cell (NPC) transplantation to the spinal cord in the absence of immunosuppression is associated with long-term survival and neuronal and glial differentiation. No tumor formation was noted. Similar cell engraftment and differentiation were shown in spinally injured transiently immunosuppressed swine leukocyte antigen (SLA)-mismatched allogeneic pigs. These data demonstrate that iPSC-NPCs can be grafted into syngeneic recipients in the absence of immunosuppression and that temporary immunosuppression is sufficient to induce long-term immune tolerance after NPC engraftment into spinally injured allogeneic recipients. Collectively, our results show that iPSC-NPCs represent an alternative source of transplantable NPCs for the treatment of a variety of disorders affecting the spinal cord, including trauma, ischemia, or amyotrophic lateral sclerosis.

• MeSH
• analýza přežití MeSH
• buněčná diferenciace MeSH
• chronická nemoc MeSH
• fibroblasty cytologie   MeSH
• homologní transplantace MeSH
• humorální imunita MeSH
• imunologická tolerance MeSH
• imunosupresivní léčba MeSH
• indukované pluripotentní kmenové buňky cytologie   MeSH
• krysa rodu Rattus MeSH
• kůže cytologie   MeSH
• mícha transplantace   MeSH
• miniaturní prasata MeSH
• neostriatum patologie   MeSH
• nervové kmenové buňky cytologie   transplantace   MeSH
• neurony cytologie   MeSH
• poranění míchy patologie   terapie   MeSH
• prasata MeSH
• přeprogramování buněk MeSH
• regulace genové exprese MeSH
• stárnutí MeSH
• transplantace izogenní MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Nuclear magnetic resonance (MR) imaging provides a noninvasive method for studying the fate of transplanted cells in vivo. We studied, in animals with a cortical photochemical lesion or with a balloon-induced spinal cord compression lesion, the fate of implanted rat bone marrow stromal cells (MSCs) and mouse embryonic stem cells (ESCs) labeled with superparamagnetic iron oxide nanoparticles (Endorem). MSCs were colabeled with bromodeoxyuridine (BrdU), and ESCs were transfected with pEGFP-C1 (eGFP ESCs). Cells were either grafted intracerebrally into the contralateral hemisphere of the adult rat brain or injected intravenously. In vivo MR imaging was used to track their fate; Prussian blue staining and electron microscopy confirmed the presence of iron oxide nanoparticles inside the cells. During the first week postimplantation, grafted cells migrated to the lesion site and populated the border zone of the lesion. Less than 3% of MSCs differentiated into neurons and none into astrocytes; 5% of eGFP ESCs differentiated into neurons, whereas 70% of eGFP ESCs became astrocytes. The implanted cells were visible on MR images as a hypointense area at the injection site, in the corpus callosum and in the lesion. The hypointense signal persisted for more than 50 days. The presence of GFP-positive or BrdU-positive and nanoparticle-labeled cells was confirmed by histological staining. Our study demonstrates that both grafted MSCs and eGFP ESCs labeled with a contrast agent based on iron oxide nanoparticles migrate into the injured CNS. Iron oxide nanoparticles can therefore be used as a marker for the long-term noninvasive MR tracking of implanted stem cells.

• MeSH
• buňky kostní dřeně metabolismus   ultrastruktura   MeSH
• elektronová mikroskopie metody   MeSH
• embryo savčí MeSH
• fosfopyruváthydratasa metabolismus   MeSH
• gliový fibrilární kyselý protein metabolismus   MeSH
• imunohistochemie metody   MeSH
• kmenové buňky metabolismus   ultrastruktura   MeSH
• komprese míchy metabolismus   patologie   terapie   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• luminescentní proteiny metabolismus   MeSH
• magnetická rezonanční tomografie metody   MeSH
• mícha cytologie   metabolismus   transplantace   ultrastruktura   MeSH
• mozek cytologie   metabolismus   ultrastruktura   MeSH
• myši MeSH
• neuroglie metabolismus   patologie   ultrastruktura   MeSH
• neurony metabolismus   patologie   ultrastruktura   MeSH
• poranění mozku metabolismus   patologie   terapie   MeSH
• potkani Wistar MeSH
• transplantace kmenových buněk metody   MeSH
• transplantace kostní dřeně metody   MeSH
• zelené fluorescenční proteiny MeSH
• železité sloučeniny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• ferric oxide MeSH Prohlížeč
• fosfopyruváthydratasa MeSH
• gliový fibrilární kyselý protein MeSH
• luminescentní proteiny MeSH
• zelené fluorescenční proteiny MeSH
• železité sloučeniny MeSH

• MeSH
• bazální ganglia transplantace   MeSH
• centrální nervový systém fyziologie   MeSH
• krysa rodu Rattus MeSH
• mícha transplantace   MeSH
• mozek MeSH
• nervová tkáň transplantace   MeSH
• periferní nervy transplantace   MeSH
• regenerace nervu * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH