Mesenchymal stem cells
Mesenchymal stem cells (MSCs) are multi-potent cells with a strong capacity for self-renewal. They are capable of multilineage differentiation into mesoderm-type cells such as osteoblast, adipocyte, chondrocyte and possibly, but still controversial, other non-mesoderm type cells, for example, neuronal cells or hepatocytes. (Abdallah et al., 2008)
They can be isolated from a variety of tissues, such as bone marrow, adipose tissue, umbilical cord, and umbilical cord blood. MSCs have the ability to differentiate into a variety of cell types, depending on cues from their microenvironment. MSCs are identified by the expression of many molecular markers, such as: CD105, CD73 and are negative for the hematopoietic markers CD34, CD45, CD14.
An important property of MSCs is their capacity for migration and homing in or around the zones damaged by ischemia, inflammation, and trauma or tumour sites. Understandably, the efficacy and time course of cell invasion into the damaged tissues depends upon the route of transplantation. (Kholodenko et al., 2013)
MSCs have great potential as therapeutic agents, since they can be obtained fairly effortlessly and can be rapidly expanded ex vivo for autologous transplantation, according to (Dharmasaroja et al, 2009).
Dr. Nirmeen Kishk and colleagues (Egypt) transplanted autologous (i.e., isolated from the patient) bone-marrow-derived mesenchymal stem cells into 43 subjects with chronic SCI. Mesenchymal stem cells have the potential to 1) differentiate into a variety of tissue types (see figure) depending upon the unique signals from the local physiological environmental, and 2) detect and migrate toward injured tissues.
MsCs for treatment of stroke
MSC therapies include cell delivery via intravenous, intracerebral or intrathecal injection. MSCs transplanted into the brain have been demonstrated to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons, as well as alter the gap junction coupling between astrocytes that allows these cells to respond more effectively to control damage (Li and Chopp, 2009).The primary trophic property of MSCs is the secretion of growth factors and other chemokines to induce cell proliferation. MSCs express mitogenic proteins such as: transforming growth factor-alpha (TGF-α), TGF-β, hepatocyte growth factor (HGF), epithelial growth factor (EGF), basic fibroblast growth factor (FGF-2) and insulin-like growth factor-1 (IGF-1). (Matthew B Murphy, 2013)
Benefits of MSCs in the ischemic brain include: transdifferentiation, induction of neurogenesis and angiogenesis, neuroprotection, and activation of endogenous neurorestorative processes, as well as decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons and regulate inflammation, primarily through paracrine actions. (Nanette Joyce et al, 2010)
(Parekkadan et al.,2010) and (Chen et al., 2001) Conclude that although the benefits of MSCs are undeniable, the homing of MSC to brain infarcted sites is far from ideal. Stem cells are attracted by stromal cell-derived factor-1α, secreted by astrocytes and endothelial cells around the infarcted region, in the ischaemic brain.(Imitola et al., 2004) In addition, matrix metalloproteinase-9 (MMP-9) is involved in the motility of stem cells by degrading components of the extracellular matrix. MMP-9 suppression reduced stem cells migration in the infarcted brain. Therefore, both stromal cell-derived factor-1α and MMP-9 expression appear to be essential for the homing ability of stem cells. (Tsai et al., 2011) The study has also found that, priming MSCs with VPA or lithium increased homing to the cerebral infarcted regions, and copriming with VPA and lithium further enhanced this effect.
Discussion
Conclusion
References
National Institutes of Health, U.S. Department of Health and Human Services. (2002). Stem Cell basics. Available: http://stemcells.nih.gov/info/basics/pages/basics1.aspx. Last accessed 15/04/2014.