In the April 8, 2014 edition of the journal Neurology, neurologist Steven Cramer, M.D. and a team from the University of California - Irvine published a meta-analysis reviewing 46 preclinical studies looking at the efficacy of stem cells in treatment of ischemic strokes. The researchers found that 44 of these studies showed significantly improved outcomes over control therapies.
Of particular interest is the fact that the effects of the stem cells on functional recovery were quite beneficial regardless of how they were delivered to the patients, the overall dosage/amount of cells given, and even the timing of treatment in relation to the stroke event. As examples, there were improved outcomes when stem cells were given a month after the stroke, and whether given via a blood vessel or injected directly into the brain. These studies were based mainly on stem cells derived from bone marrow, but adipose (fat) derived stem cells should at least show similar promise, if not more.
Of note, the stem cells that are administered do not appear to actually develop, or differentiate, into neural cells. Thus, the stem cells are not actually replacing the damaged cells by turning into new neural cells. Instead, the stem cells modulate the immune system and help the overall healing process. Stem cells release a wide array of growth factors and chemicals that help to stop damage already occurring in cells, increase the growth of new cells, stimulate growth of a new vascular supply, protect cells at risk, and improve the connective tissue that supports the neural tissue. It is in these ways that the outcomes are greatly improved.
Although all of the studies looked at were preclinical, meaning not actual treatment or trials on humans, the overall results are quite compelling. The next step will be clinical trials on human patients that will then start to define the best practices for the use of stem cells, including ideal timing and dosage.
Tuesday, August 19, 2014
Wednesday, August 6, 2014
The Biology of Wound Healing
I have received questions in regards to the mechanism of wound healing, and how stem cells play a part. This entry is (hopefully) an easy-to-understand lesson in the biology behind the process. Please feel free to pose any other questions to me and I will do my best to answer!
I will focus on the healing process of the skin, or the dermis. In general, there are four overlapping phases to dermal wound healing: 1. coagulation/hemostasis 2. inflammatory response 3. cell proliferation 4. remodeling.
Hemostasis starts once the initial injury occurs, compromising the integrity of the underlying blood vessels. As blood escapes from these vessels, platelets interact with collagen and other extracellular matrix substances. It is these stimulated platelets that begin the clotting cascade and release clotting factors and inflammatory cytokines.
The inflammatory phase starts within hours of the initial insult, mainly as neutrophils enter the fibrin clot in response to the cytokines. They are followed by leukocytes and macrophages which work together to neutralize foreign substances and help to sterilize the wounded tissue. It is also during this phase that stem cells are activated by pro-inflammatory mediators. Stem cells modulate the immune response and can help inhibit the activity of mast cells and natural killer cells. In this way, stem cells can attenuate the acute immune response. The inflammatory environment also stimulates stem cells to upregulate prostaglandin E2, favoring dermal tissue regeneration. In summary, stem cells favor wound healing over inflammation, while helping to promote functional regeneration during the next phase.
The proliferation phase begins as these immune cells recruit local reparative cells (including more stem cells) from the surrounding area to form what is called granulation tissue. This granulation tissue is well-vascularized, meaning it has a substantial blood supply, and acts as a scaffold for tissue regeneration. Eventually this is what allows for the wound bed to heal and close off. Stem cells help encourage the construction of a viable vascular supply, through the release of many growth factors.
The process concludes with the remodeling phase, wherein cells called fibroblasts help reorganize the extracellular matrix to reinforce the early granulation tissue and also to produce proteins that help regenerate the skin tissue. Stem cells express certain factors that help in this phase to promote growth of healthy and functioning dermal tissue, tissue that resembles uninjured tissue as opposed to scar tissue.
By understanding this entire process and the role stem cells play in it, we can then use a patient's own stem cells to help in the acute healing process. Stem cells directly applied to or injected into a wound can help with healing through multiple mechanisms, adding to their own injury response. There is also accumulating evidence that stem cells given systemically through an IV will find the injured area through complex signaling and still impart a regenerative effect.
I hope this explanation is not too scientific and not overly filled with "medicalese". If so, please let me know....
I will focus on the healing process of the skin, or the dermis. In general, there are four overlapping phases to dermal wound healing: 1. coagulation/hemostasis 2. inflammatory response 3. cell proliferation 4. remodeling.
Hemostasis starts once the initial injury occurs, compromising the integrity of the underlying blood vessels. As blood escapes from these vessels, platelets interact with collagen and other extracellular matrix substances. It is these stimulated platelets that begin the clotting cascade and release clotting factors and inflammatory cytokines.
The inflammatory phase starts within hours of the initial insult, mainly as neutrophils enter the fibrin clot in response to the cytokines. They are followed by leukocytes and macrophages which work together to neutralize foreign substances and help to sterilize the wounded tissue. It is also during this phase that stem cells are activated by pro-inflammatory mediators. Stem cells modulate the immune response and can help inhibit the activity of mast cells and natural killer cells. In this way, stem cells can attenuate the acute immune response. The inflammatory environment also stimulates stem cells to upregulate prostaglandin E2, favoring dermal tissue regeneration. In summary, stem cells favor wound healing over inflammation, while helping to promote functional regeneration during the next phase.
The proliferation phase begins as these immune cells recruit local reparative cells (including more stem cells) from the surrounding area to form what is called granulation tissue. This granulation tissue is well-vascularized, meaning it has a substantial blood supply, and acts as a scaffold for tissue regeneration. Eventually this is what allows for the wound bed to heal and close off. Stem cells help encourage the construction of a viable vascular supply, through the release of many growth factors.
The process concludes with the remodeling phase, wherein cells called fibroblasts help reorganize the extracellular matrix to reinforce the early granulation tissue and also to produce proteins that help regenerate the skin tissue. Stem cells express certain factors that help in this phase to promote growth of healthy and functioning dermal tissue, tissue that resembles uninjured tissue as opposed to scar tissue.
By understanding this entire process and the role stem cells play in it, we can then use a patient's own stem cells to help in the acute healing process. Stem cells directly applied to or injected into a wound can help with healing through multiple mechanisms, adding to their own injury response. There is also accumulating evidence that stem cells given systemically through an IV will find the injured area through complex signaling and still impart a regenerative effect.
I hope this explanation is not too scientific and not overly filled with "medicalese". If so, please let me know....
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