Curating Ultra-Precise Cells to Treat Spinal Cord Injuries

The spinal cord—a long tube of tissue that runs from the brain to the lower back—carries nerve signals from the brain to the rest of the body. Known as the information highway of the human body, these signals allow people to feel sensations, breathe, and move their limbs. Spinal cord injuries (SCI) are complex and varied; an injury to the upper spinal cord near the neck might look very different from an injury to the lower spinal cord. These injuries sever the brain’s connection to the body and, unfortunately, have no cure.  

Nisha Iyer, Tiampo Family Assistant Professor of Biomedical Engineering, uses stem cells to study developmental biology and regenerative medicine to understand and advance the repair of neural injuries like SCI. Iyer was recently awarded a grant from the Craig H. Neilsen Foundation’s Spinal Cord Injury Research on the Translational Spectrum (SCIRTS) program to study how creating spinal stem cells that match the specific location and types of cells found along the spinal cord could potentially accelerate SCI recovery. 

Using stem cells to address SCI treatment challenges 

Stem cells can morph into different cell types and self-renew, unlike somatic cells—the specialized cells in muscle, heart, retina, or skin that carry out one function and rarely divide. While adult stem cells regenerate only their own tissue—e.g., blood, skin, and gut lining—and neural tissue is largely off-limits; the neurons a person starts with are essentially the ones they keep for life. Pluripotent stem cells, by contrast, can become any cell type. Human induced pluripotent stem cells (hiPSCs) are somatic cells reprogrammed to an embryonic-like state, restoring their potential to turn into anything, including the spinal neurons adult tissue can't regenerate.  

“Because of their complexity, spinal cord injuries are currently the ‘Holy Grail’ of regenerative medicine and tissue engineering,” Iyer explained. “My lab is interested in applying hiPSCs’ potential to regenerate spinal cord tissue and help restore functionality after injury.”   

SCI is complex to treat because of how cell types differ based on function and location along the spinal cord, which is composed of many different cell types, each with roles that vary by position. Some neurons are sensory, relaying stimuli like touch and pain, while others are motor, driving movement. A motor neuron in the upper cord may look much like its counterpart in the middle or lower cord, but its genetics differ. Those differences let it wire onto distinct partner cells in the body and throughout the spinal cord and brain.   

“People have been trying to use embryonic stem cells and hiPSCs to cure spinal cord injuries for the past 26 years since we’ve had access to them in the late 1990s,” explained Iyer. “With this grant, our lab is asking—what if researchers aren’t making the right type of cells?” 

The SCIRTS grant will allow Iyer’s lab to use hiPSCs to make spinal stem cells that mimic different cell types (i.e., sensory vs. motor) and SCI locations (i.e., upper, middle, lower spinal cord)—a level of precision that has not been achieved before. Their hypothesis is that by creating, for example, a motor neuron cell that “thinks” it’s from the lower back, a patient might better recover from SCI in that area. 

Speeding up recovery and treatment advancements 

Because SCI treatment involves neurology, engineering, surgery, and more, it requires an interdisciplinary approach to study and understand. Iyer will collaborate with Timothy O’Shea, Assistant Professor of Biomedical Engineering at Boston University, to conduct transplantation experiments. They will also explore whether chemically stimulating grafts that have been engineered to “turn on” in response to a designer drug might promote faster regeneration and recovery. 

“If we can engineer the cells to become integrated faster or deliver drugs, maybe we can also engineer their impact,” Iyer said. 

Iyer also noted that the first clinical trials testing the impact of stem-cell therapies for SCI are currently unfolding, which could make it easier for advancements to move from the lab to the clinic with processes and pipelines already in place. Beyond applications in SCI, this research could serve as a powerful foundation to help investigate similar hypotheses for other kinds of neurological conditions, including degenerative diseases of the spinal cord like amyotrophic lateral sclerosis or multiple sclerosis, which progress differently in patients depending on the spinal region. 

“The ultimate goal of the work is to better understand how different cell therapies may have different value for different patients,” Iyer said. “This research will help us get one step closer to figuring out how to personalize treatments and speed up how fast patients can take back control of the critical functions they really care about.” 

The long-term vision of the Iyer Stem Cell & Regeneration Lab is to utilize advances in stem cell biology and emerging engineering technologies to develop personalized therapeutic strategies for neural repair. Learn more about Iyer’s lab.  

Supporting a wide range of research, the Craig H. Neilsen Foundation’s SCIRTS portfolio advances studies aimed at improving function, testing new treatment strategies, and moving them forward to improve outcomes for individuals with SCI. Learn more about the Craig H. Neilsen Foundation and SCIRTS.