results. The study demonstrates that administering adult autologous bone marrow-derived stem cells via multiple routes is feasible, safe, and, most importantly, improves the quality of life for both acute and chronic spinal cord injury (SCI) patients. The study documents the first eight of 52 patients (four acute and four chronic) who were administered autologous bone marrow-derived stem cells using a multiple route delivery technique. A two-year follow-up was performed on these first eight patients.
Using sequential MRIs, the follow-up demonstrated noticeable morphological changes within the spinal cord after administration of autologous stem cells. Participating spinal cord injury patients experienced varying degrees of improvement in their quality of life, such as increased bladder control and regained mobility and sensation. Most importantly, the study demonstrated no adverse effects, such as tumor formation, increased pain, and/or deterioration of function following administration of autologous stem cells.
Mesenchymal stem cells (MSCs) are adult stem cells traditionally found in the bone marrow. However, mesenchymal stem cells can also be isolated from other tissues, including cord blood, peripheral blood, fallopian tube, and fetal liver and lung. Multipotent MSCs differentiate to form adipocytes, cartilage, bone, tendons, muscle, and skin. TCA Cellular Inc. has found some success in preclinical animal studies showing that infusing bone marrow-derived mesenchymal stem cells into the spinal fluid may contribute to improving neurologic function in animal models with spinal cord injuries. Based on encouraging preclinical (animal) studies a Phase 1 clinical trial of autologous bone marrow-derived mesenchymal stem cells in patients with spinal cord injury have been started with expected enrollment of 10 subjects. The primary objective of the trial is to assess the safety, and the secondary objective is to see if the treatment can provide functional improvement in neuromuscular control and sensation in affected areas.
Despite the tremendous promise of using stem cells for treating spinal cord injury, there are also limitations of an ethical and practical nature. For example, the source (embryonic versus adult), the risk of tumor formation, cell availability, the need for immunosuppression, and the potential to differentiate into the wrong tissues are all important considerations. Ongoing research is attempting to address these and other challenges while taking stock of the wishes of patients living with spinal cord injuries.
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.
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