Reprogrammed stem cell-derived neurons survive long-term in pigs with spinal cord injuries

May 9, 2018, University of California - San Diego
Reprogrammed stem cell-derived neurons survive long-term in pigs with spinal cord injuries
A population of induced pluripotent stem cell-derived neurons in an allogenic, previously injured spinal cord of a pig at 3-and-a-half months. Credit: UC San Diego Health

A major hurdle to using neural stem cells derived from genetically different donors to replace damaged or destroyed tissues, such as in a spinal cord injury, has been the persistent rejection of the introduced material (cells), necessitating the use of complex drugs and techniques to suppress the host's immune response.

In a new paper, publishing May 9 in Science Translational Medicine, an international team led by scientists at University of California San Diego School of Medicine describe successfully grafting induced (iPSC)-derived neural precursor cells back into the spinal cords of genetically identical adult pigs with no immunosuppression efforts. The grafted cells survived long-term, displayed differentiated functionality and caused no tumors.

The researchers also demonstrated that the same cells showed similar long-term survival in adult pigs with different genetic backgrounds after only short course use of immunosuppressive treatment once injected into injured .

"The promise of iPSCs is huge, but so too have been the challenges. In this study, we've demonstrated an alternate approach," said senior author Martin Marsala, MD, professor in the Department of Anesthesiology at UC San Diego School of Medicine and a member of the Sanford Consortium for Regenerative Medicine.

"We took skin cells from an adult pig, an animal species with strong similarities to humans in spinal cord and central nervous system anatomy and function, reprogrammed them back to stem cells, then induced them to become (NPCs), destined to become nerve cells. Because they are syngeneic—genetically identical with the cell-graft recipient pig—they are immunologically compatible. They grow and differentiate with no immunosuppression required."

Co-author Samuel Pfaff, PhD, professor and Howard Hughes Medical Institute Investigator at Salk Institute for Biological Studies, also noted: "Using RNA sequencing and innovative bioinformatic methods to deconvolute the RNA's species-of-origin, the research team demonstrated that pig iPSC-derived neural precursors safely acquire the genetic characteristics of mature CNS tissue even after transplantation into rat brains."

In their study, researchers grafted NPCs into the spinal cords of syngeneic non-injured pigs with no immunosuppression. The researchers found that the NPCs survived and differentiated into neurons and supporting glial cells at all observed time points. The grafted neurons were detected functioning seven months after transplantation.

Then researchers grafted NPCs into allogeneic (genetically dissimilar ) with chronic , followed by a transient four-week regimen of immunosuppression drugs. They found similar results with long-term cell survival and maturation.

"Our current experiments are focusing on generation and testing of clinical grade human iPSCs, which is the ultimate source of cells to be used in future clinical trials for treatment of spinal cord and central nervous system injuries in a syngeneic or allogeneic setting," said Marsala.

"Because long-term post-grafting periods—one to two years—are required to achieve a full grafted -induced treatment effect, the elimination of immunosuppressive treatment will substantially increase our chances in achieving more robust functional improvement in spinal trauma patients receiving iPSC-derived NPCs."

"In our current clinical cell-replacement trials, immunosuppression is required to achieve the survival of allogeneic cell grafts. The elimination of immunosuppression requirement by using syngeneic cell grafts would represent a major step forward" said co-author Joseph Ciacci, MD, a neurosurgeon at UC San Diego Health and professor of surgery at UC San Diego School of Medicine.

Explore further: Researchers use human neural stem cell grafts to repair spinal cord injuries in monkeys

More information: J. Strnadel el al., "Survival of syngeneic and allogeneic iPSC–derived neural precursors after spinal grafting in minipigs," Science Translational Medicine (2018). stm.sciencemag.org/lookup/doi/ … scitranslmed.aam6651

Related Stories

Researchers use human neural stem cell grafts to repair spinal cord injuries in monkeys

February 26, 2018
Led by researchers at University of California San Diego School of Medicine, a diverse team of neuroscientists and surgeons successfully grafted human neural progenitor cells into rhesus monkeys with spinal cord injuries. ...

Using donor stem cells to treat spinal cord injury

August 28, 2017
A new study in mice published in The Journal of Neuroscience details a potential therapeutic strategy that uses stem cells to promote recovery of motor activity after spinal cord injury.

Dramatic growth of grafted stem cells in rat spinal cord injuries

August 7, 2014
Building upon previous research, scientists at the University of California, San Diego School of Medicine and Veteran's Affairs San Diego Healthcare System report that neurons derived from human induced pluripotent stem cells ...

It's not a rat's race for human stem cells grafted to repair spinal cord injuries

August 28, 2017
More than one-and-a-half years after implantation, researchers at University of California San Diego School of Medicine and the San Diego Veterans Administration Medical Center report that human neural stem cells (NSCs) grafted ...

Neural stem cell therapies could eventually play a role in treating spinal cord injuries

May 4, 2017
Researchers in Qatar and Egypt, working with colleagues in Italy and the US, have found that injured spinal cords in rats show signs of tissue regeneration several weeks following injection with neural stem cells.

Biphasic electrical stimulation: A strategy may bring hope to spinal cord injury patients

August 24, 2013
Researchers at the Beihang University School of Biological Science and Medical Engineering, led by Dr. Yubo Fan, have discovered that Biphasic Electrical stimulation (BES), a non-chemical procedure, may be used as a strategy ...

Recommended for you

Brain response study upends thinking about why practice speeds up motor reaction times

August 16, 2018
Researchers in the Department of Physical Medicine and Rehabilitation at Johns Hopkins Medicine report that a computerized study of 36 healthy adult volunteers asked to repeat the same movement over and over became significantly ...

Newly identified role for inhibition in cerebellar plasticity and behavior

August 16, 2018
Almost everyone is familiar with the unique mixture of surprise and confusion that occurs after making a mistake during an everyday movement. It's a fairly startling experience—stumbling on a step or accidentally missing ...

Men and women show surprising differences in seeing motion

August 16, 2018
Researchers reporting in the journal Current Biology on August 16 have found an unexpected difference between men and women. On average, their studies show, men pick up on visual motion significantly faster than women do.

How people use, and lose, preexisting biases to make decisions

August 16, 2018
From love and politics to health and finances, humans can sometimes make decisions that appear irrational, or dictated by an existing bias or belief. But a new study from Columbia University neuroscientists uncovers a surprisingly ...

Working memory might be more flexible than previously thought

August 16, 2018
Breaking with the long-held idea that working memory has fixed limits, a new study by researchers at Uppsala University and New York University suggests that these limits adapt themselves to the task that one is performing. ...

Protein droplets keep neurons at the ready and immune system in balance

August 15, 2018
Inside cells, where DNA is packed tightly in the nucleus and rigid proteins keep intricate transport systems on track, some molecules have a simpler way of establishing order. They can self-organize, find one another in crowded ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.