Putnam Valley, NY. (Oct. 13, 2014) – Two studies recently published in Cell Transplantation reveal that cell transplantation may be an effective treatment for spinal cord injury (SCI), a major cause of disability and paralysis with no current restorative therapies.
Using laboratory rats modeled with SCI, researchers in Spain found in laboratory tests on cells harvested from rats - specifically ependymal progenitor cells (epSPCs), multipotent stem cells found in adult tissues surrounding the ependymal canal of the spinal cord - responded to a variety of compounds through the activation of purinergic receptors P2X4, P2X7, P2Y1 and P2Y4. In addition, the epSPCs responded to adenosine triphosphate (ATP) through this activation. ATP, a chemical produced by a wide variety of enzymes that works to transport energy within cells, is known to accumulate at the sites of spinal cord injury and cooperate with growth factors that induce remodeling and repair.
"The aim of our study was to analyze the expression profile of receptors in ependymal-derived neurospheres and to determine which receptors were functional by analysis of intercellular Ca2+ concentration," said study co-author Dr. Rosa Gomez-Villafuertes of the Department of Biochemistry at the Veterinary School at the University of Complutense in Madrid, Spain. "We demonstrated for the first time that epSPCs express functional ionotropic P2X4 and P2X7 and metabotropic P2Y1 and P2Y4 receptors that are able to respond to ATP, ADP and other nucleotide compounds."
When they compared the epSPCs from healthy rats to epSPCs from rats modeled with SCI, they found that a downregulation of P2Y1 and an upregulation of P2Y4 had occurred in the epSPCs in the SCI group.
"This finding opens an important avenue for potential therapeutic alternatives in SCI treatments based on purinergic receptor modulation," the researchers concluded.
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The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1257_Gomez_Villafuertes.
Contact: Dr. Rosa Gomez-Villafeurtes, Department of Biochemistry, Veterinary School, University of Complutense, Av. Puerta de Hierro s/n, 28040, Madrid, Spain.Email: marosa@vet.ucm.esPh: +34913943890Fax: + 34913943909
Citation: Gómez-Villafuertes, R.; Rodríguez-Jiménez, F. J.; Alastrue-Agudo, A.; Stojkovic, M.; Miras-Portugal, M. T.; Moreno-Manzano, V. Purinergic receptors in spinal cord-derived ependymal stem/progenitor cells and its potential role in cell-based therapy for spinal cord injury. Cell Transplant.Appeared or available online: July 15, 2014
Spinal cord injury results in demyelination of surviving axons and impairment of motor and sensory function. In a second study on cell transplantation and SCI, a combined Egyptian/U.S. research team from Cairo University and Rutgers University's Robert Wood Johnson Medical School discovered that transplanted and manipulated adherent, autologous (self-donated) bone marrow cells (ABMCs), when transplanted into dogs modeled with SCI, augmented the remyelination process and enhanced neurological repair of the damaged area. They used bone marrow cells because bone marrow is known to contain multiple cell types that contribute differently to injury repair.
"Our study demonstrated that the transplantation of autologous canine ABMCs contributed considerably to the inadequate axonal regeneration resulting from SCI," said Dr. Hatem E. Sabaawy of the Regenerative and Molecular Medicine Program at the Robert Wood Johnson Medical School at Rutgers University. "These data were in accordance with the beneficial effects seen with ABMC transplantation in humans with SCI as based on the outcome of our Phase I/II clinical trial."
The researchers noted that it was possible that ABMCs or their derivative cells are reprogrammed in the body (in vivo) to adapt to or exhibit a remyelinating fate "in response to clues in the SCI microenvironment."
"Further studies of each of these potential mechanisms of repair will shed light on the roles of ABMCs in mediating SCI repair and allow for defining targets for an added enhancement of these repair features to achieve a more significant neural regeneration," they concluded.
The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-0904_Gabr.
Contact: Dr. Hatem E. Sabaawy, Regenerative and Molecular Medicine Program, Robert Wood Johnson School of Medicine, Rutgers University. 195 Little Albany St., New Brunswick, NJ 08901, USA.Email: sabaawhe@rutgers.eduPh: 732-235-8081Fax: 732-235-8681
Citation: Gabr, H.; El-kheir, W. A.; Farghali, H. A. M. A.; Ismail, Z. M. K.; Zickri, M. B.; El Maadawi, Z. M.; Kishk, N. A.; Sabaawy, H. E. Intrathecal transplantation of autologous adherent bone marrow cells induces functional neurological recovery in a canine model of spinal cord injury. Cell Transplant.
Appeared or available online: July 15, 2014
"These two studies highlight the increasing evidence demonstrating that a variety of different types of stem cells could have benefit in the treatment of spinal cord injury" said Dr. Shinn-Zong Lin, professor of Neurosurgery and superintendent at the China Medical University Hospital, Beigang, Taiwan and Coeditor-in-chief of Cell Transplantation. "The first study highlights a potentially important role of purinergic receptors and neural stem cells in regenerative therapy, while the second study demonstrates benefit using autologous bone marrow cells that can be relatively easily obtained in a larger animal model than rodents."
Source: Cell Transplantation Center of Excellence for Aging and Brain Repair