Survival of syngeneic and allogeneic iPSC–derived neural precursors after spinal grafting in minipigs

Authors	STRNADEL Jan CARROMEU Cassiano BARDY Cedric NAVARRO Michael PLATOSHYN Oleksandr GLUD Andreas N. MARSALA Silvia KAFKA Jozef MIYANOHARA Atsushi KATO JR. Tomohisa TADOKORO Takahiro HEFFERAN Michael P. KAMIZATO Kota YOSHIZUMI Tetsuya JUHAS Stefan JUHASOVA Jana HO Chak-Sum KHERADMAND Taba CHEN PeiXi BOHAČIAKOVÁ Dáša HRUSKA-PLOCHAN Marian TODD Andrew J. DRISCOLL Shawn P. GLENN Thomas D. PFAFF Samuel L. KLIMA Jiri CIACCI Joseph CURTIS Eric GAGE Fred H. BUI Jack YAMADA Kazuhiko MUOTRI Alysson R. MARSALA Martin
Year of publication	2018
Type	Article in Periodical
Magazine / Source	Science Translational Medicine
MU Faculty or unit	Faculty of Medicine
Citation
Web	http://stm.sciencemag.org/content/10/440/eaam6651.short
Doi	http://dx.doi.org/10.1126/scitranslmed.aam6651
Keywords	cells derived; iPSC
Description	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.