Potential Stem-Cells Based Therapeutics

This is taken from a discussion I participated in regarding potential uses of stem cells to treat incurable diseases such as multiple scelerosis that I found particularly interesting:

Multiple sclerosis is an autoimmune disease of the central nervous system characterized by damaged myelin sheath. The myelin coating around axons of nerve cells allows for the nervous system to function properly. Damage to the myelin sheath is caused by attack from the body’s immune system. The cause of MS is unknown; it is thought that the disease could occur due to genetic mutation or from a viral infection.


Specific stem cells with regulatory properties of the immune system are thought to have a potential benefit for use in MS treatment. Stem cells, such as mesenchymal stem cells (MSCs), could help prevent the immune system to continue to attack the integrity of the myelin sheath of the CNS when used in therapy. This can assist in delaying disease progression. In this type of therapy, adult stem cells are harvested from the patient’s own body (bone marrow), human umbilical cord, and bone marrow. Both MSCs and T regulatory cells are embedded inside of the harvested tissue, and later isolated from fat tissues. 

Neural stem/precursor cells (NPCs), derived from the CNS, are also being used for therapeutic applications in MS treatments. These stem cells can serve to protect the myelin sheath from immune system attack.

MS currently has no cure, and treatments serve to delay progression of the disease, but none consistently so. Some scientists believe that the use of stem cells in MS treatment has the most potential for discovering a cure or reliable treatment to effectively alleviate suffering from patients and increase quality of life.  

Recent research has suggested stem cells from the brain carrying the CD140 protein, a protein that makes up oligodendrocytes, which often form myelin, are the most superior candidates for MS treatment with stem cells. This would allow the restoration of damaged myelin throughout the CNS. A doctor from Rochester Medical Center, currently involved in research in this area, stated: “These cells are our best candidates right now for someday helping patients with M.S., or children with fatal hereditary myelin disorders…These cells migrate more efficiently throughout the brain, and they myelinate other cells more quickly and more efficiently than any other cells assessed thus far. Now we finally have a cell type that we think is safe and effectivie enough to propose clinical trials”( 4). 

 Jennifer Gutierrez Rodriguez”


(1) MS Research Australia, http://www.msra.org.au/living-ms

(2) PubMedHealth, USNLB, Multiple Scelrosis, http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001747/

(3) Baron Van Evercooren A, Franklin R, Kerr D, Martino G, Stem cell transplantation in multiple sclerosis: current status and future prospects, Nature Reviews Neurology 6, 247-255, May 2010http://www.nature.com/nrneurol/journal/v6/n5/abs/nrneurol.2010.35.html

(4) News Medical, Brain stem cell treatment for multiple sclerosis, http://www.news-medical.net/news/20111015/Brain-stem-cell-treatment-for-multiple-sclerosis.aspx

Induced Pluripotent Stem Cells

In order to avoid the ethical issues of using embryonic stem cells, an alternative method was found and involves using induced pluripotent stem cells (iPSCs).  iPSCs are derived from adult somatic cells that have already differentiated by reprogramming them back genetically to an undifferentiated embryonic stem cell-like state.  This is accomplished by inducing the expression of factors and genes that characterize the properties of natural pluripotent stem cells.  The expression of 4 transcription factors, Oct4, Sox2, Klf4, and cMyc, have been found to be sufficient to revert somatic cells like fibroblasts in mice back to pluripotent stem cells.
This method is relatively recent, with the first iPSCs from mice being reported in 2006 and from human cells in late 2007.  While the generation of iPSCs as a stem cell research tool is very promising in terms of getting around the ethical issues surrounding the use of embryos, there are various challenges and issues with iPSCs as well.  I will briefly describe a couple of pros and cons:
– iPSCs have the capability to divide in an umlimited fashion in culture and also to maintain the potential to differentiate into many cell types by giving arise of any of the three germ layers.
– iPSCs can be derived from a patient’s own cells, making them a valuable tool for developing therapies for various diseases as well as modeling human diseases.
– The use of viral vectors is used to deliver the reprogramming factors to the adult cells which presents some problems such as insertional mutagenesis leading to developmental abnormalities in the cells.
– Elevated mutation rate induced by the stress incurred from reprograming the cells.
– Studies with iPSCs so far showed yields of iPSCs from somatic cells that are as low as 0.1% with higher yields being only around 1-3%.  This low efficiency presents some challenges for clinical applications of iPSCs.
– Unknown differences between iPSCs and natural pluripotent stem cells
Ling Phoun  (edited by Y. S. Hassan)

1.  Weinacht et al.  The role of induced pluripotent stem cells in research and therapy of primary immunodeficiencies.  Current opinion in immunology. Epub ahead of print, published online 25 July 2012.
2.  Lei et al.  Directed differentiation of induced pluripotent stem cells towards T lymphocytes. J Vis Exp. 2012 May 14;(63):e3986. doi: 10.3791/3986.
3.  Park et al. Generation of human-induced pluripotent stem cells. (2008) Nat Protoc. 3(7):1180-6.
4. Ji J et al. Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells. Stem Cells. 2012 Mar;30(3):435-40. doi: 10.1002/stem.1011.