Research ArticleSpinal Cord Injury

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

See allHide authors and affiliations

Science Translational Medicine  09 May 2018:
Vol. 10, Issue 440, eaam6651
DOI: 10.1126/scitranslmed.aam6651

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Stem cell transplants in pigs with spinal cord injury

Neural precursor cells (NPCs) hold promise for treating spinal cord injury (SCI). Testing viability and engraftment properties of NPC transplants in large-animal models is necessary for understanding the clinical potential of this approach. In a new study, Strnadel et al. transplanted syngeneic and allogeneic induced pluripotent stem cell–derived NPCs (iPSC-NPCs) into the spinal cords of naïve pigs and animals with SCI. The transplanted cells showed a good safety profile, long-term survival, and differentiation into mature neurons and glial cells. Successful engraftment of allogeneic iPSC-NPCs required only temporary immunosuppression, an important consideration for the future clinical evaluation of iPSC-NPCs for treating SCI.

Abstract

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.

View Full Text