Mesenchymal Stem Cells for the Management of Stroke: Mesenchymal stem cells (MSCs, also called bone marrow stromal cells) are found in the bone marrow and represent 0.001-0.01% of its total nucleated cells. MSCs are isolated from a bone marrow aspirate, which is often collected from the superior iliac crest of the pelvis. MSCs are different from hematopoietic stem cells which is another stem cell class of the bone marrow. MSCs are multipotent stem cells that can differentiate into a variety of body cells such as osteoblasts, chondrocytes, myocytes, adipocytes, fibroblasts, and neurons. MSCs have been shown to enhance the regeneration mechanisms of the central nervous system. In the brain, they can differentiate into astrocytes, endothelial cells, and neurons. In addition, MSCs secrete neurotrophic factors such as NGF, BDNF, VEGF, and bFGF. Furthermore, MSCs decrease the thickness of the glial scar, reduce the number of the glial microglia/macrophages, and promote glial-axonal remodeling after stroke. Systemically administered MSCs successfully homed to the rat brain after traumatic brain injury, selectively localized around the injury and partially expressed immature neuronal marker Tuj1 and an astrocytic marker, GFAP (glial fibrillary acidic protein).
Thus, the cumulative effect of transplanting MSCs into the infarcted brain is amplifying neurogenesis, synaptogenesis, and angiogenesis and enhancing the overall process of neural repair and regeneration. In a study done by Bang OY et al. (2005) in South Korea, intravenous culture-expanded autologous MSCs showed improvement of functional recovery in stroke patients. The procedure was shown to be safe and well tolerated. Interestingly, allogenic cells can be used as MSCs do not induce immune-mediated rejection reactions.
Mesenchymal Stem Cells and Parkinson's Disease: MSCs have been used to treat Parkinson's disease (PD) in animal models. Intrastriatal injection of MSCs in MPTP mouse model of PD showed survival of the transplanted cells that expressed tyrosine hydroxylase (a rate-limiting enzyme in dopamine biosynthesis) with reduced motor dysfunction.
Mesenchymal Stem Cells and Spinal Cord Injury: MSCs have been explored for the management of spinal cord injury (SCI). Local injection of MSCs one week after the SCI resulted in the formation of nerve fiber-permissive tissue bridges across the epicenter of the lesion filled with debris and macrophages. The mesenchymal stem cellular graft survived and managed to produce long-term functional recovery. These effects could not be achieved when the stem cells were implanted immediately after injury.
Mesenchymal Stem Cells and Peripheral Nerve Injury: MSCs have shown beneficial effects on peripheral nerve injury. MSCs (treated by certain factors) differentiated into Schwann cells-like cells which led to vigorous nerve fiber regeneration when transplanted to the site of sciatic nerve injury. Myelination of the regenerating fibers was also observed.
References:
- Bang OY, Lee JS, Lee PH, Lee G (2005): Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol. 57: 874-82.
- Chen J, Chopp M (2006): Neurorestorative treatment of stroke: cell and pharmacological approaches NeuroRx. 3: 466-73.
- Dezawa M, Takahashi I, Esaki M, Takano M, Sawada H (2001) Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. Eur J Neurosci. 14: 1771-6.
- Hofstetter CP, Schwarz EJ, Hess D, Widenfalk J, El Manira A, Prockop DJ, Olson L (2002): Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci U S A. 99: 2199-204
- Kan I, Melamed E, Offen D (2005) Integral Therapeutic Potential of Bone Marrow Mesenchymal Stem Cells Current Drug Targets.6: 31-41.
- Li Y, Chen J, Wang L, Zhang L, Lu M, Chopp M (2001) Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Neurosci Lett. 316: 67-70.
- Phinney DG, Isakova I (2005): Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm. 11: 1255-65.
- Yi Li, Jieli Chen, Chun Ling Zhang, Lei Wang, Dunyue Lu, Mark Katakowski, Qi Gao, Li Hong Shen, Jing Zhang, Mei Lu, Michael Chopp (2005) Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells.Glia.49: 407:417.
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