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Bone Marrow Stem Cells

Bone Marrow Stem Cells (BMSCs) are characterized as the most primitive form of stem cells that are derived from bone marrow tissue. The three types of stem cells comprising bone marrow are hematopoietic stem cells, mesenchymal stem cells, and endothelial stem cells. Bone marrow stem cells were once thought to only express the capability to differentiate into cells of the blood system. Recent findings have come to demonstrate BMC’s ability to self-renew and differentiate to cell types of all cell lineages (1, 2, 3). Scientists have now come to believe these stem cells can help in restoring structure and function of damaged cells within the body. Opponents of this view consider many controversial points coming from this research which has recently slowed the progress of this field.

Bone Marrow Stem Cell Types

Hematopoietic stem cells (HSCs) give rise to all of the blood cell types found in circulation including leukocytes, erythrocytes, and thrombocytes (3). They are responsible for the production and renewal of blood cells. HSCs are cells isolated from the blood or bone marrow that can self-renew, differentiate into specialized cells, mobilize out of bone marrow into circulating blood, and undergo programmed cell death, also known as apoptosis (2). These cells are currently being used in regeneration of damaged cells in patients of post myocardial infarction.

Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into a wide variety of cell types. MSCs are capable of differentiation into osteoblasts, chondrocytes, and adipocytes both in vitro and in vivo (2). MSCs have the ability to differentiate into non-marrow tissues such as muscle and neural tissues. Morphologically, mesenchymal stem cells have long thin cell bodies with a large nucleus. These cells have a high capacity for self-renewal and multipotency. The degree to which the culture will differentiate varies among individuals and how differentiation is induced chemically vs. mechanically, and it is not clear whether these variations due to the degree of true progenitor cells in the population or variable differentiation capacities of individual progenitor cells. It is known that the capacity for a cell to proliferate and differentiate decreases with age (2).

Endothelial Stem Cells are a controversial and hypothetical population of rare cells believed to circulate in the blood and have the ability to differentiate into cells of the endothelium, the thin layer lining the blood vessels. Research is currently being done to provide more evidence for this theory but if these cells were to exist in adults, they would be believed to be angioblasts, or stem cells that form blood vessels during the process that embryo is formed. Other beliefs indicate these stem cells play a part in the formation of skin cells.

Significance

Bone marrow stem cells are generally less flexible and versatile compared to stem cells of the embryo. Embryonic (or fetal) stem cells have greater differentiation potential because of their pluripotency. The social and ethical controversy surrounding stem cell research stimulates opposition among pro-life advocates who believes the research devalues life and takes a step in the direction of reproductive cloning. Recent findings suggest adult stem cells may be capable of differentiating into a range of specialized cell types. Adult stem cells are rare in tissue and pose a challenge in harvesting, taking into account the large quantity of cells needed for stem cell therapies (4). However, there remains no knowledge of whether an embryonic stem cell will be rejected from the body. Adult stem cells taken from a patient’s own cells can be isolated in culture, grown to assume a specific cell type, and reintroduced back into the patient, with low risk of attack from the immune system (4).

A recent study demonstrates BMC’s ability to regenerate dead cells of the myocardium post-myocardial infarction (2). BMC’s give rise to cardiac myocytes and coronary blood vessels weeks after transplanted into infarct mouse models (2). In the CNS, BMC’s enhance endogenous recovery mechanisms and facilitate neuronal plasticity (5). These mechanisms are associated with neurogenesis, gliogenesis, and synaptogenesis. Another finding suggests BMC’s ability to insulate damaged neural cells to help initiation of cell repair and proliferation (5).

Potential Treatments

Researchers are currently developing therapies for patients affected by myocardial infarction. BMCs injected into the myocardium adjacent to the injured area mobilize to the area of damage when treated with cytokines, giving rise to new cardiac myocytes and coronary vessels (2). Another study helping in the development of new therapies for patients of traumatic brain injuries involve engraftment of BMC’s to the damaged area. Findings confirmed stem cell proliferation and regeneration within the damaged areas and their contribution to reversal of behavioral dysfunction and cytological damage (5).

The major goal for researchers in treating severe life changing neurological diseases such as Parkinson’s or Huntington’s disease comes about in generating large sources of cells to be stored and harvested in the lab. Scientists are investigating behavior of stem cells in culture and studying the mechanisms that govern dopamine, Acetylcholine (Ach), and GABA neuron production during development in attempts to identify optimal culture conditions to allow stem cells to turn into neurotransmitter-producing neurons(5).

Controversy

Countless animal trials have been run which led to many breakthroughs in the field, yet there have been an equal amount of failures. One big issue involves the reliability of some of the protocols used within each study. There is currently no knowledge of the mechanisms that account for transdifferentiation involving stem cells of the bone marrow (5). Safety and ethics are also a major issue the closer this research gets to clinical practices. There are currently no technologies available to monitor and control differentiation before and after bone marrow transplantation. The complex microenvironment of the body makes it difficult to fully predict the outcome of the cell differentiation.

Challenges

Steps are being taken in order to gain a more concrete understanding of the complexity of this type of cell behavior, what factors play a part in the specific behaviors they exhibit, and how they can be controlled both ex and in vivo. A recent study suggests expression patterns unique to donor cells that can influence heterogeneity and its influence on transdifferentiation mechanics. Researchers are also looking into constructing different technologies that would mimic the conditions inside the body that play a key role in understanding the interactions and processes involved in differentiation. Other areas of focus include more detailed analysis of soluble factors that play a key role in multipotency behavior, reengineering of synthetic material niches, and tissue-derived matrices to ensure safety and efficacy.

References

(1) Baker, Andrew H. "Brain Protection Using Autologous Bone Marrow Cell, Metalloproteinase Inhibitors, and Metabolic Treatment in Cerebral Ischemia." Proceedings of the National Academy of Sciences of the United States of America, 104.9 (2007): 3597-602. Http://www.jstor.org/stable/25426695. National Academy of Sciences, 27 Feb. 2007. Web. 7 Feb. 2010. <http://www.jstor.org/stable/pdfplus/25426695.pdf>.

(2) Orlic, Donald, Jan Kajstura, and Stefano Chimenti. "Bone Marrow Stem Cells Regenerate Infarcted Myocardium." Pediatric Transplantation 3rd ser. 7 (2003): 86-88. Wiley Interscience. Blackwell Munksgaard, 24 Mar. 2010. Web. 24 Mar. 2010. <http://www3.interscience.wiley.com/cgi-bin/fulltext/118897161/PDFSTART>.

(3) "Hematopoietic Stem Cells [Stem Cell Information]." NIH Stem Cell Information Home Page. 6 Apr. 2009. Web. 24 Mar. 2010. <http://stemcells.nih.gov/info/scireport/chapter5.asp>.

(4) "What Are the Similarities and Differences between Embryonic and Adult Stem Cells? [Stem Cell Information]." NIH Stem Cell Information Home Page. 30 Mar. 2009. Web. 24 Mar. 2010. <http://stemcells.nih.gov/info/basics/basics5.asp>.

(5) Farin, Azadeh, Charles Y. Liu, and Iver A. Langmoen. "Biological Restoration of Central Nervous System Architecture and Function: Part 3- Stem Cell- And Cell-Based Applications and Realities in the Biological Management of Central Nervous System Disorders: Traumatic, Vascular, and Epilepsy Disorders." Neurosurgery 65.5 (2009): 831-59. Restoration of Central. Congress of Neurological Surgeons, 24 Apr. 2009. Web. 18 Feb. 2010. <www.neurosurgery-online.com>.