Tuesday, May 15, 2012

Intravenous Stem Cells: Where Do They Go? What Do They Do?

We usually think of stem cell therapy in terms of replacing damaged cells or tissues with stem cells, which can differentiate and become the type of cell or tissue which is being replaced. But there is more to it than that, particularly in the case of intravenous stem cell infusion.
Researchers have tracked the migration of stem cells administered intravenously following an injury. At first the majority of the cells lodge within the lung, where they appear to interact with pulmonary macrophages altering the type of cell signaling molecules those macrophages release into the blood. Next the stem cells migrate to the organs of the reticuloendothelial system which includes the spleen. Surprisingly, less than 3% of infused stem cells migrate into brain tissue. So the immunomodulatory effect does not require the majority of infused stem cells to interact directly with injured brain tissue. _SciAm
It turns out that much of the beneficial effect from the intravenous infusion of stem cells comes from their effect on the immune system. IV infused stem cells apparently shift the immune system's response to injury and rejuvenation, creating a more favourable environment for healing and regeneration.

This allows the few stems cells which make it all the way to the damaged tissue, to promote regeneration locally without a harmful immune response.
Immunomodulatory stem cell studies attempt to adjust the immune response in a way that minimizes the damage associated with the initial injury, and then allows the individual’s native repair machinery to function optimally.

With even mild injury, the immune system is activated. Macrophages are a type of immune cell which participate in the post-injury immune response. With “classic” macrophage activation, the immune response is aggressively induced. Classically activated macrophages are described as having an “M1” phenotype. In the nervous system, the M1 immune response can increase the severity of an injury. Alternatively activated or “M2” macrophages, are associated with a less destructive pattern of immune system activation. This alternate/M2 response results in less immune mediated post-injury damage, as well as the possible disinhibition of native nervous system repair.

Following traumatic brain injury (TBI) children experience a loss of 12-15% of their brain tissue in the 12 months following their injury (Levin). In a study where we treated TBI children with their own bone marrow stem cells, there was minimal post injury brain volume loss in the year after TBI (Cox). In animal models of TBI, animals that experienced injury were found to have M1 macrophages throughout their injured brain tissue.

Animals treated with stem cells after TBI were found to have M2 macrophages in their brain parenchyma. Interestingly, if an animal’s spleen was removed before stem cell infusion, the benefit of the stem cell treatment was eliminated. Somehow stem cell infusion causes a change in the pattern of macrophage activation from M1 to M2, which results in a less aggressive immune response and less post-injury brain tissue death. This effect requires an intact spleen. _SciAm
So you see that in an optimal response to stem cell infusion following an injury, the patient will experience both immunomodulatory effect and a regenerative effect from the IV stem cell infusion.

When the stem cells being infused are of a broad-spectrum nature -- such as cord blood, embryonic stem cells, or pluripotent adult stem cells -- the door is wide open for other effects beyond the immunomodulatory and the regenerative (replacement) effects. It should be clear that other rejuvenative effects are also possible from broad spectrum stem cell infusion. It will simply require a good deal of research and consideration before most of those effects can be discovered and decoded for optimal therapies in the future.

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