Syed A. Quadri
Desert Regional Medical Center, Palm Springs
Shariq Nawab
Sajid S. Suriya
Fahad Mehmood
Dow University of Health Sciences
Muhammad Junaid Uddin Zaheer
Aga Khan University Hospital
See Also: Adult Stem Cells: Overview; Clinical Trials Outside the United States; Geron Corporation; Neuralstem, Inc.; Spinal Cord Injury; University of Texas Health Science Center at Houston.
Further Readings
Baumgartner, James E. “Autologous Stem Cells for Spinal Cord Injury (SCI) in Children.” Memorial Hermann Healthcare System http://clinicaltrials.gov/ct2/show/NCT01328860?term=Spinal+Cord+injury+stem+cells+United+states&rank=2 (Accessed October 2014).
Gold, Joseph. “Clinical Data Update From GRNOPC1 Spinal Cord Injury Trial” http://ir.geron.com/phoenix.zhtml?c=67323&p=irol-newsArticle&ID=1635760 (Accessed October 2014).
Scadden, David T. and M. H. Raaijmakers. “Overview of Stem Cells.” uptodate.com http://www.uptodate.com/contents/overview-of-stem-cells?source=search_result&search=stem+cells+in+spinal+cord+injury&selectedTitle=1%7E150 (Accessed October 2014).
Clinical Trials, U.S.: Stroke
Clinical Trials, U.S.: Stroke
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Clinical Trials, U.S.: Stroke
Ischemic stroke occurs due to blockage in blood flow due to a clot or narrowing in an artery. Brain cells deprived of oxygen normally die within minutes. Stroke is one of the most common causes of death in the United States, with over 750,000 cases per year. More commonly, it leads to permanent debilitation. Today, the most widely used treatments are various medications (thrombolytic agents: tPA) and endovascular interventions, often combined with physical and/or speech therapy. With the exception of rehabilitation therapy, very few treatments are available to improve the chronic neurologic deficits caused by a stroke. In addition to medication and physical therapy, there is promising research on the benefits of stem cell treatments for stroke victims. Some stem cell treatments would facilitate or improve the recovery and rehabilitation after a stroke, while other stem cell research focuses on the ability to repair damage done during a stroke.
Stem cells (SCs) are characterized by their ability for self-renewal (i.e., maintaining their undifferentiated state during several rounds of cell division), and their potency (i.e., the ability to differentiate into specialized cell types). The two main stem cell types are embryonic stem cells (ES) and adult stem cells (i.e., somatic stem cells). Other types, such as induced pluripotent stem cells (iPSCs), are produced in the lab by reprogramming adult cells to express ES characteristics. Mesenchymal stem cells (MSCs) are a subset of adult stem cells from bone marrow or adipose tissue. These cells are of medical and therapeutic interest because they have been shown to differentiate into osteoblasts, adipocytes, chondrocytes, myocytes, astrocytes, oligodendrocytes, and neurons.
Neural stem cells (NSCs) are one of the subtypes of adult SCs, which are particularly found in the brain of both fetal and adult mammals with the ability of differentiation to three major central nervous system (CNS) cell types: neurons, astrocytes, and oligodendrocytes.
Mechanism of Tissue Repair
Two strategies are presented to diminish an ongoing degenerative process or immunological attack. One is the transplantation of SCs to supply new neurons into the infarcted brain by the activation of intrinsic neural stem cells (NSCs) or delivery of extrinsic SCs such as embryonic stem cells (ESCs) and induce pluripotent stem (iPS) cells–derived neural cells. The second approach is usage of SCs by preparing immunomodulatory and neuroprotective support in a transplanted graft.
The first of these strategies is endogenous (meaning inside the body) repair. The idea behind endogenous repair is to stimulate stem cells that are already present in the brain to heal damaged tissue. The brain has its own store of stem cells. These are “hidden,” as if in reserve. Studies have shown that neural precursor cells (stem cells and their progeny) will proliferate and differentiate into more mature cells in response to growth factors, many of which continue to be tested in rodent models of stroke. Scientists are also looking to mobilize other endogenous stem cells to come out of their hiding places in the body and help with the aftermath of stroke. They have found that the growth factor G-CSF can mobilize hematopoietic stem cells from the bone marrow to enter the bloodstream. From the blood, the cells track to the areas of brain damaged by stroke.
The second strategy is exogenous (meaning outside the body) transplantation, whereby stem cells are harvested, purified, and then partially or completely differentiated prior to being transplanted into patients. The exogenous repair strategy harnesses the power of stem cells from a different angle than the endogenous strategy. Rather than stimulating resident stem cells into action, stem cells are first harvested from patients or donors and then manipulated in the lab prior to being transplanted into a patient. The harvested stem cells can be purified and expanded in number and partially or completely differentiated into progeny of the type required to repair damaged tissue.
A stroke is the loss of brain function due to a disturbance in the blood supply to the brain by either a lack of blood flow caused from a blockage or by hemorrhaging. A stroke was the second most frequent cause of death worldwide in 2011–taking the lives of 6.2 million people. (Blausen Medical Communications)
Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering. One of regenerative medicine’s greatest goals is to develop new treatments for stroke. Many researches are being conducted around the globe on using stem cells as a therapy for stroke. The following is a review of major researches being conducted at various universities in the United States.
University of Miami Miller School of Medicine
In the past, it was thought that stem cells would regenerate into new neurons, the cells in the brain, but it is now becoming quite clear that especially stem cells that are from the bone marrow play more of a nursing function in that they stimulate the body’s own mechanisms of repair and enhance them and make them work harder to get the repair done much better than if the stem cells were not present. They act like small factories, secreting a number of substances that stimulate the brain surrounding the injured environment and help with recovery. The first two stroke patients had been enrolled in a phase 2 clinical trial of a revolutionary new treatment for ischemic stroke being conducted at the University of Miami/Jackson Memorial Hospital in 2013.
The trial, using a patient’s own bone marrow stem cells, was the first intra-arterial stroke stem cell trial in the United States. The trial examined the efficacy of ALD-401,