Stem Cell Treatments for Spinal Cord Injuries
Stem Cells and Spinal Cord Injury:
Spinal cord injuries are described at various levels of "incomplete", which can vary from having no effect on the patient to a "complete" injury which means a total loss of function.
Treatment of spinal cord injuries starts with restraining the spine and controlling inflammation to prevent further damage. The actual treatment can vary widely depending on the location and extent of the injury. In many cases, spinal cord injuries require substantial physical therapy and rehabilitation, especially if the patient's injury interferes with activities of daily life.
STEM CELLS USED FOR SPINAL CORD INJURY
After a spinal cord injury, many of the nerve fibers at the injury site lose their insulating layer of myelin. As a result, the fibers are no longer able to properly transmit signals between the brain and the spinal cord contributing to paralysis. Unfortunately, the spinal cord lacks the ability to restore these lost myelin-forming cells after trauma.
Tissue engineering in the spinal cord involves the implantation of scaffold material to guide cell placement and foster cell development. These scaffolds can also be used to deliver stem cells at the site of injury and maximize their regenerative potential.
When the spinal cord is damaged—either accidentally (car accidents, falls) or as the result of a disease (multiple sclerosis, infections, tumors, severe forms of spinal bifida, etc.)—it can result in the loss of sensation and mobility and even in complete paralysis.
STEM CELL RESEARCH
Adult stem cell transplants for spinal cord injury repair: current state in preclinical research.
Hernándeza J, Torres-Espína A, Navarro X.
Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
Spinal cord injury (SCI) is a traumatic disorder resulting in a functional deficit that usually leads to severe and permanent paralysis. After the initial insult to the spinal cord, additional structure and function are lost through an active and complex secondary process. Since there is not effective treatment for SCI, several strategies including cellular, pharmacological and rehabilitation therapies have been approached in animal models.
Some of them have been proved in clinical trials. In this review we focus on the current state of cell therapies, particularly on cells from adult origin, assayed in preclinical research. Cell types used in SCI therapy include Schwann cells, olfactory ensheathing cells and adult stem cells, such as neural stem cells, umbilical cord blood derived cells, mesenchymal stem cells or induced pluripotent stem cells.
There are not yet conclusive evidences on which types of glial or adult stem cells are most effective in SCI treatment. Their ability to incorporate into the damaged spinal cord, to differentiate into neural lineages, to exert neuroprotective effects, to promote regeneration of damaged axons, and to improve functional deficits are still discussed, before translation towards clinical use, as a single therapy or in combination with other strategies.
Significant clinical, neuropathological and behavioural recovery from acute spinal cord trauma by transplantation of a well-defined somatic stem cell from human umbilical cord blood.
2011 Sep 8. [Epub ahead of print]
Schira J, Gasis M, Estrada V, Hendricks M, Schmitz C, Trapp T, Kruse F, Kögler G, Wernet P, Hartung HP, Müller HW.
Source Molecular Neurobiology Laboratory, Department of Neurology, Heinrich-Heine-University Medical Centre Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.
Stem cell therapy is a potential treatment for spinal cord injury and different stem cell types have been grafted into animal models and humans suffering from spinal trauma. Due to inconsistent results, it is still an important and clinically relevant question which stem cell type will prove to be therapeutically effective. Thus far, stem cells of human sources grafted into spinal cord mostly included barely defined heterogeneous mesenchymal stem cell populations derived from bone marrow or umbilical cord blood.
Here, we have transplanted a well-defined unrestricted somatic stem cell isolated from human umbilical cord blood into an acute traumatic spinal cord injury of adult immune suppressed rat. Grafting of unrestricted somatic stem cells into the vicinity of a dorsal hemisection injury at thoracic level eight resulted in hepatocyte growth factor-directed migration and accumulation within the lesion area, reduction in lesion size and augmented tissue sparing, enhanced axon regrowth and significant functional locomotor improvement as revealed by three behavioural tasks (open field Basso-Beattie-Bresnahan locomotor score, horizontal ladder walking test and CatWalk gait analysis).
To accomplish the beneficial effects, neither neural differentiation nor long-lasting persistence of the grafted human stem cells appears to be required. The secretion of neurite outgrowth-promoting factors in vitro further suggests a paracrine function of unrestricted somatic stem cells in spinal cord injury.
Given the highly supportive functional characteristics in spinal cord injury, production in virtually unlimited quantities at GMP grade and lack of ethical concerns, unrestricted somatic stem cells appear to be a highly suitable human stem cell source for clinical application in central nervous system injuries.
Neural tissue engineering using embryonic and induced pluripotent stem cells.
Stem Cell Res Ther. 2011 Apr 15;2(2):17
Authors: Willerth SM
ABSTRACT: With the recent start of the first clinical trial evaluating a human embryonic stem cell-derived therapy for the treatment of acute spinal cord injury, it is important to review the current literature examining the use of embryonic stem cells for neural tissue engineering applications with a focus on diseases and disorders that affect the central nervous system. Embryonic stem cells exhibit pluripotency and thus can differentiate into any cell type found in the body, including those found in the nervous system.
A range of studies have investigated how to direct the differentiation of embryonic cells into specific neural phenotypes using a variety of cues to achieve the goal of replacing diseased or damaged neural tissue.
Additionally, the recent development of induced pluripotent stem cells provides an intriguing alternative to the use of human embryonic stem cell lines for these applications. This review will discuss relevant studies that have used embryonic stem cells to replicate the tissue found in the central nervous system as well as evaluate the potential of induced pluripotent stem cells for the aforementioned applications.
PMID: 21539726 [PubMed - as supplied by publisher]
Stem cell therapy and coordination dynamics therapy to improve spinal cord injury.
Electromyogr Clin Neurophysiol. 2008 Jun-Jul;48(5):233-53
Authors: Schalow G
During competition a motocross athlete suffered a clinically complete spinal cord injury (SCI) at the Thoracic 11/12 levels according to MRIs (magnetic resonance imaging). Six weeks after the accident the subject began intensive Coordination Dynamics Therapy (CDT) at an up-to-date therapy centre.
After 6 months of therapy, when further improvements were only marginal, the patient opted for haematopoietic stem cell therapy in addition to ongoing CDT. During two years of stem cell therapy, including 4 sessions of stem cell application, and ongoing coordination dynamics therapy, improvement remained marginal--no more than what would have been achieved with continuing only CDT.
It is concluded that this haematopoietic stem cell therapy did not have any beneficial effect on the repair of the spinal cord in this patient. Differences in the regeneration capacity between commonly used laboratory animals and human are addressed. On the basis of a frog model for regeneration, cell communication, and neural control, it is discussed why complete SCI in human are difficult to improve and why for stem cell therapies more proper human knowledge is needed to induce structural repair and direct it to the injured sites of the neuronal networks.
Further research is needed to improve and justify the clinical application of stem cell therapy. A thoughtful combination of stem cell therapy and CDT may have a chance of structural repair even in complete SCI. However, objective measures are needed to quantify improvement in MRI (anatomic measure), EMG (measuring of motor programs by sEMG, electrophysiologic measure), and measurements of coordination dynamics (kinesiologic measure).
Stem Cell Treatments and Spinal Cord Injuries NIH database search and results:
Related Articles Rolipram potentiates bevacizumab-induced cell death in human glioblastoma stem-like cells. Life Sci. 2017 Feb 12;: Authors: Ramezani S, Vousooghi N, Kapourchali FR, Hadjighasem M, Hayat P, Amini N, Joghataei MT Abstract AIMS: Glioblastoma cancer stem-like cells (GCSCs) promote themselves proliferation by secreting the vascular endothelial growth factor A (VEGFA) in an autocrine manner, positively regulated by phosphodiesterase IV (PDE4). In the current study, we investigated the putative cytotoxic effect of bevacizumab, a VEGFA blocker, alone and in combination with a specific inhibitor of PDE4 called rolipram on GCSCs isolated from human surgical tumor specimen with a focus on PI3K/AKT pathway. MAIN METHODS: CD133+/CD15+ GCSCs were characterized by flow cytometry and expanded in a serum-free primary culture system. The cell survival, apoptosis, and protein expression values were measured using MTT assay, TUNEL staining and western blot, successively. Intracellular cAMP and free secreted VEGFA levels were assessed by cAMP enzyme immunoassay and ELISA, respectively. KEY FINDINGS: Bevacizumab suppressed GCSCs survival with IC50~6.5μg/ml and enhanced the levels of apoptosis, p53 and cleaved-caspase3 along with a decrease in free VEGFA levels and ERKs activation. However, there was no significant modulation of AKT phosphorylation on serine 473, the intracellular PDE4A, VEGFA and cAMP levels. More cytotoxicity in co-treated cells coupled with a more substantial decline in the free VEGFA levels and a greater increase in the quantities of p53 and cleaved-caspase3 compared to those treated with bevacizumab alone. Co-treatment reduced phospho-AKT, endogenous VEGFA and PDE4A values but elevated cAMP levels. SIGNIFICANCE: This study highlighted a booster cytotoxic effect of combined rolipram and bevacizumab treatment on the GCSCs primary culture, suggesting that this approach is warranted in treatment of GBMs overexpressing VEGFA and PDE4A. PMID: 28202289 [PubMed - as supplied by publisher]Read more...