(Boston, MA)- In the recent PNAS Early Edition, researchers from Spaulding Rehabilitation Network and Harvard Medical School reported their findings on a new research project that developed a polymer-based platform for the delivery of human bone marrow mesenchymal stromal stem cells (hMSCs) to the lesion site of adult rat spinal cord injury (SCI), and demonstrated that the hMSC delivery platform promoted hMSC survival, stemness and function characteristics without cell differentiation that led to motor and sensory improvement, myelin preservation, and neuropathic pain and tissue damage alleviation. The treatment worked mainly through protecting and activating neural pathways within the spinal cord. This could mean a new way of thinking, new formula to transplant adult stem cells that can be directly obtained from individuals with SCI to avoid immune rejection, and new way of healing. The study led by Dr. Ted (Yang D.) Teng and Dr. Ross Zafonte at Spaulding could have translational impact on approaches to developing clinical rehabilitation therapies that target the newly uncovered cellular, molecular and nerve pathway targets for people with spinal cord injury conditions.
“Our research focuses on obtaining functional recovery after spinal cord injury by using integrated strategies that involve stem cells, biomaterials, and pharmacological compounds to identify neural networks for repair and activation. Such a novel approach has shown encouraging results for laying down ground for us to define a new concept of “Recovery Neurobiology” that describes the ability of the spinal cord and brain, under proper treatment, to use neural circuits that are different from healthy situations to recover function after trauma,” says Dr. Teng, Associate Professor of Physical Medicine & Rehabilitation and Neurosurgery at Harvard Medical School and Director of SCI Research, VABHS.
Previous studies of hMSC-mediated neural repair relying on either stem cell alone implantation or “neural transdifferentiation” of hMSCs are inconclusive due to technical barriers of poor donor survival, non-defined donor cell location and very limited donor-host interaction. In this study researchers first tailored a unique poly acid scaffold that, emulating proper extracellular niche, could maintain hMSC stemness and augment hMSC survival and function in the adult spinal cord. Our investigators designed their unique polymer scaffolding system via characterizations utilizing an original organotypic dorsal root ganglio co-culture system, buoyed by their earlier success of investigating a biodegradable polymer implant co-developed with MIT scientists. The further refined version of polymer implant has now been approved by FDA for a potential therapeutic benefit clinical trial for acute traumatic SCI.
Dr. Zafonte, Charlton Professor and Chair in Physical Medicine and Rehabilitation at Harvard Medical School and Vice President Medical Affairs at Spaulding said of the study, pointed out that “This novel approach advances the field and provides future additional approach to facilitate function after Spinal Cord Injury.”
The study’s findings suggest that reconnections of the corticospinal tract with the spinal cord segment below injury level may not be essential for partial locomotion restoration. The current conventional approach also emphasizes that all stem cell types (including embryonic and induced pluripotent cells) will need to be pre- differentiated toward a neural phenotype, or in some way manipulated to emulate the “gold- standard” cell destination before transplantation in order to fulfill cell replacement requirement in the CNS. By contrast, this study built upon previous findings of neural recovery resulting from neural progenitor cell treatment without neuronal replacement (e.g., Teng et al., PNAS99:3024, 2002 for spinal cord injury and Sci Transl Med 4:165, 2012 for ALS). The implications of this study for the broader field of adult stem cell-based regenerative neuroscience and medicine are important. Instead of trying to use healthy adult human neural pathway as the only blueprint to repair the spinal cord or brain, the reported data suggested that researchers and physicians should also look into how to identify unconventional neural circuits that can be harnessed for recovering function of the targeted motor or sensory system.
The bench study of this project was mainly carried out by four equal contribution postdoctoral fellows in Dr. Teng’s laboratory who have now moved onto their next career stage successfully. Dr. Teng and Dr. Zafonte also collaborated with Dr. Richard Sidman, Bullard Professor of Neuropathology, Emeritus of Harvard Medical School. The project was primarily funded by Veterans Affairs Rehab R&D, DoD, CASIS-NASA and a grant from the Cele H. and William B. Rubin Family Fund.
About the Spaulding Rehabilitation Hospital
Founded in 1971, Spaulding Rehabilitation Hospital in Boston is one of the largest rehabilitation facilities in the United States, and is ranked the 5th top rehabilitation hospital in the country by U.S. News & World Report. As the official teaching hospital of the Harvard Medical School Department of Physical Medicine and Rehabilitation (PM&R), Spaulding is at the forefront of research in advances in rehabilitative care. In April 2013, Spaulding opened a new 132-bed facility in Charlestown which is a national model for environmental and inclusive design. With a wide range of inpatient programs and 25 outpatient centers throughout Eastern Massachusetts, Spaulding strives to continually update and improve its programs to offer patients the latest, high-quality care through its leading, expert providers. Spaulding has been awarded a Model Systems designation in three specialty areas- Brain Injury, Spinal Cord Injury and Burn Injury Rehabilitation- by the National Institute on Disability, Independent Living, and Rehabilitation Research. For more information, please visit www.spauldingrehab.org
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