Bone-Marrow Stromal Cells for Repair of Spinal Cord

A Novel Three-Pronged Cellular Therapy for Progressive Multi-Stage MS Patients:
©2013, Keesee WW et al

Does Bone marrow transplantation (BMT) represent a novel therapy for the amelioration and even cure for multiple sclerosis (MS)? Can a combination biologic tissue engineered neural matrix, repair and regenerate new myelin, restoring the electrical connections in the patients damaged spinal cord? Do chronic wounds in the geriatric MS population trigger a never ending cycle of autoimmune response? What advanced therapies are available in skin and wound care? There is a need for a paradigm shift in our thinking about the pathogenesis and the distinct possibilities/benefits of combination approaches in multiple sclerosis therapies. Most scientists working in laboratories, far from the trenches of clinical applications and the endless suffering of patients, only see very limited aspects of specific molecular, cellular and /or genetics usually involved in new drug
development. Unfortunately this has resulted in little to no game changing medical breakthroughs.
Here we appear to be the first recorded in published literature to have observed clinically, the three main elements of this problem and now propose a combined therapy as a new approach. This involves reprogramming the body’s self- destructive autoimmune software which allows/tricks the immune system to relentlessly attack and destroy the myelin sheath that results in paralysis. The next problem: So we can reset /regenerate a new immune system, but that alone will not routinely repair the previously destroyed neurons and myelin. We need to be exploring the best combination neural biologics and self-assembling nano-matrix cocktails, for direct injection into the diseased and destroyed tissues, thereby regenerating new neurons and the requisite myelin. Finally, we have observed that chronic wounds in the aging population appear to be a causative factor, self-perpetuating the infected auto-immune system to over-react, in perpetuity. Are there any fresh ideas in chronic wound care?
 Abstract
Bone marrow transplantation (BMT) potentially represents a novel therapy for the amelioration and even cure for multiple sclerosis (MS). It has important advantages over immunosuppressive drug treatments because, while effecting broad-based ablation of the immune system and over-reactive cells, it provides an important means for overcoming the resultant immunodeficiency, while possibly restoring self-tolerance. Due to the heterogeneity of the disease, current immunosuppressive and modulatory treatments have shown only partial efficacy in ameliorating the course of MS. Bone marrow transplantation (BMT) therapies that aim to eliminate pathogenic immune cells by broad based immune ablation regimens decrease the severity and progression of disease in some MS patients who no longer responded to conventional treatments. According to Dr. Louis Rosner, “For treatment of multiple sclerosis (MS), early positive signals began with a few leukemia patients who also had MS. Their bone-marrow transplants not only helped their battles with leukemia, their MS symptoms improved as well.
Richard K. Burt, MD concurs with this adding, “The fate of some patients with MS has propelled us to consider more aggressive intervention. Immune ablation with hematopoietic stem cell rescue for these patients is no longer a theoretical or academic discussion. Three institutions (Northwestern University, Medical College of Wisconsin, and the University of Indiana) have IRB-approved protocols to perform immune ablation and T-cell depleted autologous hematopoietic stem cell rescue in patients with rapidly progressive MS.”
Neural Matrix: Strategies for regenerating the adult CNS with a combination tissue engineering neural matrix Stem cells have been recognized and intensively studied for their potential use in restorative approaches for degenerative diseases and traumatic injuries. In the central nervous system (CNS), stem cell-based strategies have been proposed to replace lost neurons in degenerative diseases , or to replace lost oligodendrocytes in demyelinating diseases such as multiple sclerosis.

Stem cells have also been implicated in repair of the adult spinal cord. An impact to the spinal cord results in immediate damage to tissue including blood vessels, causing loss of neurons, astrocytes, and oligodendrocytes. In time, more tissue nearby or away from the injury site is lost due to secondary injury. In case of relatively minor damage to the cord some return of function can be observed, but in most cases the neurological loss is permanent.
A substantial effort in cellular regeneration research has focused on identifying suitable cell types for replacing lost neurons and the proliferation and differentiation capabilities of those cells.
However, the vast majority of cells implanted do not survive, and those that do survive do not fully integrate, failing to couple electrically or mechanically.
So what is the answer? Why do most of the implanted cells die?

Bioengineered Scaffolds for Neuroregeneration

Tissue engineering has rapidly evolved in the past decade into an integrating discipline in which every organ forms a science of tissue engineering: Each of these sciences are interfacing with different scientific communities, including
biotechnology, biopharmaceutical manufacturing , chemical engineering, cell biology, developmental biology, gene therapy, medical sciences, and organic chemistry.
Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include new neurons, glia, axons and myelin.
As a result of a high incidence of neurological injuries, nerve regeneration and repair, a subfield of neural tissue engineering, is a rapidly growing field dedicated to the discovery of new ways to recover nerve functionality after injury.
In people who have multiple sclerosis, the immune system attacks the nerve cells or neurons, in the brain and/or spinal cord. Neurons consist of a cell body, which receives impulses from other neurons and that produces impulses, and an axon, which is attached to the cell body and which carries the impulses to other neurons. All of the nervous tissue in the body, including the brain and spinal cord, functions through this communication between neurons.
Many neurons have multiple layers of a protein and lipid substance surrounding their axons---this substance is called myelin. The neurons that have myelin are referred to as "myelinated" neurons, and the myelin that surrounds their axons is called a myelin sheath. The myelin sheath protects the axon. The immune system of a person who has MS attacks the myelin sheaths, producing scars or plaques, which are also called scleroses. The destruction of myelin interferes with, and can eventually destroy, the neuron's ability to send signals to other neurons. The scar tissue is permanent, and damaged neurons cannot be repaired.
Chronic Wounds in Older Adults and their Relationship to Auto-Immune Responses in MS Patients.
The rate and quality of wound healing depend on etiology, size, anatomical location, and comorbid conditions. Clearly, the older adult population is more likely to have developed more comorbid conditions throughout a lifetime, which can directly cause a wound or have a negative impact on wound healing.
There continues to be a controversy around the issue of whether pressure ulcerations are an expected outcome of neurodegenerative disorders that cause progressively worsening mobility or whether they are a completely avoidable occurrence.
One of the most common complications of a chronic wound is infection, whether superficial or deep in nature. All chronic wounds are contaminated with bacteria. The way the body's host defenses respond to the bacteria, however, is the primary determinant of whether infection will occur. If the infection is deep, it is unlikely that wound healing will occur without the use of antimicrobial agents, locally and systemically. It is estimated that about a quarter of all persons with chronic wounds are receiving antibiotics at any one time, and 60% of patients with chronic wounds have received systemic antibiotics within the previous 6 months.

We propose that the safety and efficacy of human tissue-engineered skin, with over 200,000 prescriptions filled and zero adverse effects reported to the FDA, is a relatively inexpensive therapy for chronic wounds. Also Fibrin sealant, or fibrin "glue," is a unique surgical hemostatic/adhesive material that is being utilized with increasing frequency in a variety of surgical situations including difficult deep wound fistula protocols. In addition, recent advances in, magnetic pulsed energy stem cell generators for skin and tissue repair, promise a non-invasive therapy with no perceivable side effects.

The following is a partial list of strategies covered: Study Shows Stem Cell Infusions are the 1st Therapy to Reverse MS; The Potential of Mesenchymal Stem Cells For Neural Repair. Therapy for MS Prods Brain to Re-Cloak Neurons. Wound healing versus regeneration: Role of the tissue environment in regenerative medicine. First Evidence that Chitosan Could Repair Spinal Damage. Bone marrow stromal cells for repair of the spinal cord: towards clinical application. Could MS nerve damage be repaired? Stem cell study in mice offers hope. Mayo Clinic uses new approach to reverse multiple sclerosis. Adult bone marrow: Which stem cells for cellular therapy protocols in neurodegenerative disorders. Infections: Many microbes have been proposed as potential infectious triggers of MS. Autologous hematopoietic stem cell transplantation for autoimmune diseases. Dr. Synkowski’s fibrin adhesive deep wound fistula protocol
Tissue engineering with mesenchymal stem cells (MSCs) Isolation and expansion; Isolation protocols; Human bone marrow-derived MSCs; Expanding human
MSCs; Genetic engineering of MSCs; Injectable biomaterials; Key factors in material selection ;Smart biomaterials; Resolutions of inflammation: An orchestrated sequence of events. Advances in Multiple Sclerosis and demyelinating diseases. Patented pulsed magnetic stem cell generators offer a powerful new therapy for tissue and bone regeneration. Combination products and final thoughts. Global Regulatory Considerations:
A Novel Three-Pronged Cellular Therapy for Progressive Multi-Stage MS Patients: ©2013, Keesee WW et al

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