SPINAL CORD INJURY: REGENERATION BY SCHWANN CELL OR PROGENITOR THERAPY AND ADVANCED CELLULAR TECHNOLOGY.
For the moment, restoration of the transected human spinal cord (quadriplegia or paraplegia) by the implantation of embryonic or adult stem cells is only a dream. Therefore, the aspirations of spinal cord injury victims, should not be raised according to BOLAND CELL .
BASIC SCIENCE REGARDING SCHWANN CELLS: RELEVANCE TO SCHWANN CELL TRANSPLANTATION
The Schwann cells (sheath cells) appear as one or more irregular flattened cells with nuclei between adjacent nodes of Ranvier in the neurilemma (Morris' Human Anatomy, 1893:931). These cells arise or are derived from the neural crest, and are part of the peripheral nervous system. These cells (SC) do not appear in the central nervous system ( brain). Schwann cells synthesize protective lipoprotein myelin, but much less than oligodendrocytes in the CNS. SC, obviously are key regulators of peripheral nerve development, including myelin sheaths (Bruska et al 1999., Folia Morphol 58 (3 suppl 2): 101-7). Spanish neuroanatomist, Cajal (1853-1934) made reference to Schwann cells. He showed the cytoplasmic bands between the outer surface of the myelin sheath and the Schwann cell plasma membrane of the Schwann cell. Absence of the bands, results in impaired impulse conduction. These bands can be demonstrated by the Cajal silver-staining of myelinated nerves (see Cajal Institute drawings: Nature 431, 191-195 (2004). The SC, of neuroectodermal origin, form a thin sleeve around the myelin, which surrounds the axon (Histology: Bloom and Fawcett, 1986: W. B Saunders Company, 330-331). SC is important for the life and function of the axons of peripheral nerve fibers. Regarding regeneration, "the new axon grows out of the proximal stump and follows the path formed by Schwann cells" (Histology: Bloom and Fawcett). Meier et al 1999 of University College London, have shown that developing Schwann cells acquire the ability to survive without axons by establishing an autocrine circuit involving ILG-F, neurotrophin-3 and platelet-derived growth factor-BB (J Neuroscience, 1999: 19: 3847-59). According to this group, "this is critically important because successful axonal regrowth in a damaged nerve depends on interactions with living Schwann cells in the denervated distal stump". SC, the regulators of nerve development (Schwann cell precursors) is controlled by a neuronally derived signal, beta neuregulin (J Physiol Paris, 2002: 96, 17-24). See also histology resources on Schwann cells (Basic Histology, Lange, 178; Histology and Cell Biology, Mosby, 207). Two types of SC are now recorded: myelinating and non-myelinating Schwann cells (Int J Biochem Cell Biol 2006; 38:1995-9). Both play a pivotal role in the maintenance and regeneration of axons of the neurons in the PNS. Krox- 20, Oct-6 and Sox-10, all neurotrophic factors, regulate Schwann cells. SC are affected in two diseases, Charcot-Marie-Tooth and Guillain-Barre Syndrome.
NERVE REGENERATION RESEARCH DATA:SCHWANN CELLS
- Transplantation of cultured adult peripheral nerve Schwann cells can partially improve intentional trauma to the corticospinal tracts (rat model).
- Transplanted SC can modify sprouting from cut central axons.
- SC is being studied as Schwann cell "bridging" repair (peripheral nerves). Very important work because the "bridges" can be used to fill in nerve defects.
- SC can invade an injured spinal cord but the timing of cell therapy is important (J Neurosci Res 1996:45, 588-97).
- University of Miami School of Medicine and researchers have demonstrated regrowth of axons in the lesioned adult rat spinal cord: promotion by implants of cultured Schwann cells. Further studies on the mini-channel model are important (Eur J Neuro Sci 1999).
- Schwann-cell implants may well play an important role in the repair strategy of spinal cord injury (Braz J Med Biol Res, 2005:38:825-35).
- Recently developed culture systems and ex-vivo technology, as described by BOLAND CELL , can provide large, highly purified populations of Schwann cells, destined for repair of the spinal cord and peripheral nerves. Special mediums and electromagnetic phototherapy as described by BOLAND CELL can enhance monolayer cell proliferation.
- In rats, transplantation of cultured Schwann cells into the subarachnoid route can improve neurological deficit (Neurosci Lett 2006, 402:66-70). This offers a hope for the patient suffering from a spinal cord injury ( severe contusion, partial or complete transsection).
SUMMARY OF BASIC SCIENCES AND CELL TECHNOLOGY: AFTER OUDEGA ET AL 2006
The Schwann cell plays a crucial role in the PNS by:
- The ability to differentiate.
- The ability to migrate.
- The ability to proliferate (in-vivo and ex- vivo).
- Express growth promoting factors.
- The ability to myelinate regeneration axons.
- Clearly then, Schwann cells have great potential for repair of the injured spinal cord, but possibly SC-transplantation (or of progenitors) may have to be combined with other interventions to maximize axonal regeneration and functional recovery (Oudega et al, J Neurotrauma 2006, 23:453-67).
POTENTIAL APPLICATION OF CULTURED SCHWANN CELL MONOLAYERS OR PROGENITORS FOR NEUROSPINAL CELL THERAPY (USING BOLAND CELL TECHNOLOGY).
- Tissue engineering of biodegradable constructs that is currently in progress ( cells plus biological membranes: with assessment of cellular differentiation and phenotype expression via tissue markers).
- Tissue engineering via nanotechnology for peripheral nerve damage replacement.
- Tissue engineering of biodegradable constructs and cells for spinal cord regeneration.
- Determining ways and means of reversing spinal die-back after spinal cord injury.
ACADEMIC HISTOLOGY AND PATHOLOGY STUDY RESOURCES
- Histology. Ham A. Lippincott, Philadelphia . 1964.
- Basic Medical Histology :The Biology of Cells, Tissues, and Organs. Kessel R. G. Oxford University Press, 1998.
- Langman's Medical Embryology . Sadler T. W. Lippincott, Williams & Wilkins, Philadelphia (Chapter 19, :433, 2004).
- Robbin's Basic Pathology : Kumar, Cotran, Robbins. 7 th Edition.Saunders, 2003, Philadelphia .