A recent study from Laura Shin and Daniel Peterson in Stem Cells Translational Medicine (2013; 2:33-42) attempts to clarify exactly how stem cells given as a treatment actually induce healing. The conventional theory has been that these cells act by differentiating once inside the body, as in they change into the cell types that the body needs to repair and heal itself. This equates to the analogy that they act as seeds that then grow into the new tissue.
However, this recent study seems to point to a different mechanism of action.The researchers used human mesenchymal stem cells in mice that were given excisional wounds that were splinted open. The splint wound model more closely duplicates how human wounds heal by granulation and re-epithelialization (rather than by skin contraction, the normal repair mechanism in rodents). The treated mice were given a pair of these wounds, one that received an engraftment of stem cells and the other left untreated. The stem cells were genetically modified so the researchers could trace the cells after giving them to the mice. There was also a control group who had similar paired wounds, but received no stem cells.
The results of this study showed that the animals that received stem cell therapy had accelerated healing when compared to the control group. However, the stem cells themselves did not seem to be the cells directly involved in the wound repair. The traced stem cells were abundantly evident in the treated wound just one day after delivery, but the numbers were dramatically reduced by day 5, and these cells were not even detectable in the wound bed by day 10.
The wounds that received no stem cells showed a rather significant delay in closure compared to those receiving stem cells. The stem cells were also only engrafted into one of the paired wounds on each treated mouse, but the non-treated wound on that mouse showed a moderate improvement in healing over the non-stem cell mice as well.
The results seem to indicate that the improved closure of the wounds despite the relatively rapid decrease in engrafted stem cell numbers may be due to signalling within the wound bed that helps to modulate and direct the host's own cells. The injected stem cells appear to recruit the patient's own stem cells to the area of injury, both at the engrafted site as well as distant sites in the body to some degree. These signals also seem to be maintained after the engrafted stem cells are gone. Thus the authors propose that while the stem cells are useful for healing, it is the subsequent healing response that they induce that ultimately leads to wound repair. If this is truly the manner that stem cells are involved in the healing process, it is the signals they produce that are the key to success with future therapies.
Tuesday, October 1, 2013
Thursday, August 1, 2013
Stem Cells From Fat Versus Bone Marrow
A recent study published in the journal "Stem Cells Translational Medicine" seems to indicate that adipose-derived stem cells are more potent than bone marrow derived cells when comparing how they each modulate the immune system.
Functionally, both cell types responded similarly. They each had the capacity to differentiate toward both osteogenic and adipogenic lineages. In terms of the immune system response, both had similar surface marker expression. However, the adipose-derived stem cells showed a significantly higher level of suppression of peripheral blood mononuclear cell proliferation when used in equal numbers. Approximately three times the number of bone marrow derived stem cells were necessary to get the same suppressive effect.
This effect appears to be related to a decrease in inflammatory cytokines and an increase in certain anti-inflammatory cytokines. Cytokines are immunomodulating agents, such as interleukins and interferons.
This marks a significant finding in using stem cells for therapeutic applications. The frequency of stem cells in bone marrow is comparatively low, with stem cells accounting for only 0.001% - 0.01% of the total mononuclear cell fraction. Also, bone marrow aspiration is relatively invasive. Adipose tissue, however, contains approximately 500-fold greater frequency of stem cells, and collection via lipoaspiration is simple and easily tolerated.
The study also showed that adipose cells secrete higher levels of a multitude of cytokines that have been implicated in how stem cells modulate our immune systems.
Because of these many factors, adipose-derived stem cells appear to be a much better choice for cell-based therapies.
-from Stem Cells Translational Medicine 2013;2:455-463
Functionally, both cell types responded similarly. They each had the capacity to differentiate toward both osteogenic and adipogenic lineages. In terms of the immune system response, both had similar surface marker expression. However, the adipose-derived stem cells showed a significantly higher level of suppression of peripheral blood mononuclear cell proliferation when used in equal numbers. Approximately three times the number of bone marrow derived stem cells were necessary to get the same suppressive effect.
This effect appears to be related to a decrease in inflammatory cytokines and an increase in certain anti-inflammatory cytokines. Cytokines are immunomodulating agents, such as interleukins and interferons.
This marks a significant finding in using stem cells for therapeutic applications. The frequency of stem cells in bone marrow is comparatively low, with stem cells accounting for only 0.001% - 0.01% of the total mononuclear cell fraction. Also, bone marrow aspiration is relatively invasive. Adipose tissue, however, contains approximately 500-fold greater frequency of stem cells, and collection via lipoaspiration is simple and easily tolerated.
The study also showed that adipose cells secrete higher levels of a multitude of cytokines that have been implicated in how stem cells modulate our immune systems.
Because of these many factors, adipose-derived stem cells appear to be a much better choice for cell-based therapies.
-from Stem Cells Translational Medicine 2013;2:455-463
Tuesday, July 16, 2013
Stem Cell Transplants and HIV Patients
I recently came across a very intriguing story about HIV patients who had undergone chemotherapy and stem cell transplants as part of lymphoma therapy. This is a story about the potential involved in stem cell treatments, and something that continues to reveal the vast array of diseases that may one day be treated this way.
The story is about HIV-positive patients who have undergone what is being called the "sterilizing cure", wherein the above-mentioned medical therapy removes all traces of the virus. These HIV-positive patients developed lymphoma that required chemotherapy followed by bone marrow transplants as a cure for the cancer. The bone marrow (stem cell) transplants effectively removed the virus from their bodies. These two patients represent the second and third known cases where the sterilizing cure has apparently worked. An earlier patient had a similar result after treatment for leukemia.
Most recently, the two patients with HIV were being treated with long-term antiretroviral therapy when they developed lymphoma. The antiretroviral medications were continued through the duration of chemotherapy and also the bone marrow transplants. After these treatments, both patients have shown no traces of virus. Lead researcher Dr. Timothy Henrich, from Harvard Medical School and Brigham and Women's Hospital in Boston, said that "we have been unable to detect virus in either the blood cells or the plasma of these patients." He also biopsied intestinal tissue from one of the patients and could not detect virus there either.
The research team withdrew the patients' antiretroviral medications in order to test how effective the cancer therapy had worked to eliminate the virus. One patient has been off medication for 15 weeks, and the other for 7 weeks, both without showing any rebound of the virus.
The researchers are not calling it a true cure as of yet, as the virus could still be present in extremely low amounts that just aren't detectable.
In bone marrow transplants, donor cells replace the host's blood cells, and in these patients, the antiretroviral medications seemed to allow the donor stem cells to replace the host cells without becoming infected with the virus.
These results were presented at the International AIDS Society Conference in Kuala Lumpur, Malaysia and are considered preliminary findings.
The story is about HIV-positive patients who have undergone what is being called the "sterilizing cure", wherein the above-mentioned medical therapy removes all traces of the virus. These HIV-positive patients developed lymphoma that required chemotherapy followed by bone marrow transplants as a cure for the cancer. The bone marrow (stem cell) transplants effectively removed the virus from their bodies. These two patients represent the second and third known cases where the sterilizing cure has apparently worked. An earlier patient had a similar result after treatment for leukemia.
Most recently, the two patients with HIV were being treated with long-term antiretroviral therapy when they developed lymphoma. The antiretroviral medications were continued through the duration of chemotherapy and also the bone marrow transplants. After these treatments, both patients have shown no traces of virus. Lead researcher Dr. Timothy Henrich, from Harvard Medical School and Brigham and Women's Hospital in Boston, said that "we have been unable to detect virus in either the blood cells or the plasma of these patients." He also biopsied intestinal tissue from one of the patients and could not detect virus there either.
The research team withdrew the patients' antiretroviral medications in order to test how effective the cancer therapy had worked to eliminate the virus. One patient has been off medication for 15 weeks, and the other for 7 weeks, both without showing any rebound of the virus.
The researchers are not calling it a true cure as of yet, as the virus could still be present in extremely low amounts that just aren't detectable.
In bone marrow transplants, donor cells replace the host's blood cells, and in these patients, the antiretroviral medications seemed to allow the donor stem cells to replace the host cells without becoming infected with the virus.
These results were presented at the International AIDS Society Conference in Kuala Lumpur, Malaysia and are considered preliminary findings.
Thursday, July 11, 2013
Organ Growth from Stem Cells
Here is an NPR story about stem cells...
http://www.npr.org/2013/07/05/199025495/building-a-liver-from-stem-cells
http://www.npr.org/2013/07/05/199025495/building-a-liver-from-stem-cells
Tuesday, May 21, 2013
Stem Cells and Brain Lesions
The current issue of the STEM CELLS Translational Medicine journal contains a study involving a novel way of increasing the survival rate of stem cells injected into the brain.
Researchers harvested neural stem cells (NSC's) from baby mice and sorted the cells to find a predominance of stem cells containing CD15, a carbohydrate found on the surface of the cells that plays a very important role in cellular migration and adhesion, and in growth factor signaling that helps in cell maintenance and differentiation. This sorting process allowed them to harvest a population of NSC's in which 98% of them were positive for the CD15 marker, approximately six times more than when the sorting method is not used.
These CD15 -positive cells were then differentiated in the lab, eventually resulting in neurons, astrocytes, and oligodendrocytes - these are specific types of cells found in our brain and spinal cord. Neurons are the cells that process and transmit information, astrocytes are the most abundant cells that provide stuctural and metabolic support, and the oligodendrocytes provide support to and insulate our nerve cells. These developed cells were then introduced into the brains of baby mice and studied over time, along with a control group of non-sorted neural cells. Initially, both groups of cells were similar in the baby mice - one week later, when the brain was still growing, the cells in both groups had achieved similar population levels. However, in adult mice the CD15-positive grafts showed significantly higher survival rates. The cells with CD15 also tended to significantly differentiate into oligodendrocytes, cells that have a protective role for neurons.
The significance of this study is that it shows a potential method for improved deliverance of therapeutic cells to our brain and spianl cord. Anthony Atala, MD, edior of the journal and director of the Wake Forest Institute for Regenerative Medicine said "the fact that the CD15-positive cells show a significant increase in oligodendrocyte differentiation suggests that they may be particularly useful for treating diseases involving white matter lesions." White matter lesions are commonly associated with Alzheimer's Disease, multiple sclerosis, and stroke. These types of lesions have also been found with infectious and inflammatory conditions, and even associated with patients experiencing migraine headaches.
Yet another bold step in the research of stem cells and possible therapeutic benefits!
Researchers harvested neural stem cells (NSC's) from baby mice and sorted the cells to find a predominance of stem cells containing CD15, a carbohydrate found on the surface of the cells that plays a very important role in cellular migration and adhesion, and in growth factor signaling that helps in cell maintenance and differentiation. This sorting process allowed them to harvest a population of NSC's in which 98% of them were positive for the CD15 marker, approximately six times more than when the sorting method is not used.
These CD15 -positive cells were then differentiated in the lab, eventually resulting in neurons, astrocytes, and oligodendrocytes - these are specific types of cells found in our brain and spinal cord. Neurons are the cells that process and transmit information, astrocytes are the most abundant cells that provide stuctural and metabolic support, and the oligodendrocytes provide support to and insulate our nerve cells. These developed cells were then introduced into the brains of baby mice and studied over time, along with a control group of non-sorted neural cells. Initially, both groups of cells were similar in the baby mice - one week later, when the brain was still growing, the cells in both groups had achieved similar population levels. However, in adult mice the CD15-positive grafts showed significantly higher survival rates. The cells with CD15 also tended to significantly differentiate into oligodendrocytes, cells that have a protective role for neurons.
The significance of this study is that it shows a potential method for improved deliverance of therapeutic cells to our brain and spianl cord. Anthony Atala, MD, edior of the journal and director of the Wake Forest Institute for Regenerative Medicine said "the fact that the CD15-positive cells show a significant increase in oligodendrocyte differentiation suggests that they may be particularly useful for treating diseases involving white matter lesions." White matter lesions are commonly associated with Alzheimer's Disease, multiple sclerosis, and stroke. These types of lesions have also been found with infectious and inflammatory conditions, and even associated with patients experiencing migraine headaches.
Yet another bold step in the research of stem cells and possible therapeutic benefits!
Tuesday, April 9, 2013
Arterial Growth
Here are 2 sets of arteriograms (or angiograms, which are x-rays taken with the use of special dyes to visualize arteries):
The left side of both images show very poor arterial blood flow in the leg due to vascular disease. These patients often end up needing amputations due to the lack of blood flow.
The right side of each image shows vastly improved arterial supply after stem cell therapy. The stem cells were injected intramuscularly, meaning into the calf and other lower leg muscles. The stem cells allow for growth of new blood vessels and essentially save these patients' limbs.
Tuesday, April 2, 2013
Case Report #1 - T. M. PATIENT UPDATE
In August of 2012 I wrote about a 35 y.o. female who was our first stem cell orthopedic injection patient (see entry "Case Report #1 - T.M."). She has continued to do extremely well after her treatment and is now over one year out from the procedure. She continues to exercise in a manner that she could not prior to her stem cell therapy, including sports, hiking, and P-90-X. She denies pain and swelling in her right knee, and reports discomfort only in her left knee which has not had a stem cell injection.
On March 7, 2013 she underwent a repeat MRI of her right knee which was then compared to a prior MRI obtained on December 8, 2011.
In the time between the studies, her only treatment was the stem cell injection into the right knee joint which was done in February of 2012. Prior to the cell therapy, this patient's pain was most prominent in the inside aspect of the knee near her knee cap, which coincides with the anterior medial meniscus.
Important excerpts of the recent radiology report read as follows:
"Comparison is made to a prior study of the right knee dated 12/8/2011."
"An improved appearance of the marrow of the distal femur and tibia is noted when compared to the prior study.
Postoperative repair of the anterior horn of the medial meniscus has occurred since the prior exam."
The radiologist did not know that this patient had stem cell therapy, but obviously could detect changes that showed improvement in her primary orthopedic issue. We are very pleased to share these MRI findings and the fact that the radiologist saw evidence of meniscal repair.
On March 7, 2013 she underwent a repeat MRI of her right knee which was then compared to a prior MRI obtained on December 8, 2011.
In the time between the studies, her only treatment was the stem cell injection into the right knee joint which was done in February of 2012. Prior to the cell therapy, this patient's pain was most prominent in the inside aspect of the knee near her knee cap, which coincides with the anterior medial meniscus.
Important excerpts of the recent radiology report read as follows:
"Comparison is made to a prior study of the right knee dated 12/8/2011."
"An improved appearance of the marrow of the distal femur and tibia is noted when compared to the prior study.
Postoperative repair of the anterior horn of the medial meniscus has occurred since the prior exam."
The radiologist did not know that this patient had stem cell therapy, but obviously could detect changes that showed improvement in her primary orthopedic issue. We are very pleased to share these MRI findings and the fact that the radiologist saw evidence of meniscal repair.
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